Paracrine Signaling by Platelet-Derived Growth Factor-CC Promotes Tumor Growth by Recruitment of Cancer-Associated Fibroblasts
Open accessAbstract
Cancer results from the concerted performance of malignant cells and stromal cells. Cell types populating the microenvironment are enlisted by the tumor to secrete a host of growth-promoting cues, thus upholding tumor initiation and progression. Platelet-derived growth factors (PDGF) support the formation of a prominent tumor stromal compartment by as of yet unidentified molecular effectors. Whereas PDGF-CC induces fibroblast reactivity and fibrosis in a range of tissues, little is known about the function of PDGF-CC in shaping the tumor-stroma interplay. Herein, we present evidence for a paracrine signaling network involving PDGF-CC and PDGF receptor-alpha in malignant melanoma. Expression of PDGFC in a mouse model accelerated tumor growth through recruitment and activation of different subsets of cancer-associated fibroblasts. In seeking the molecular identity of the supporting factors provided by cancer-associated fibroblasts, we made use of antibody arrays and an in vivo coinjection model to identify osteopontin as the effector of the augmented tumor growth induced by PDGF-CC. In conclusion, we establish paracrine signaling by PDGF-CC as a potential drug target to reduce stromal support in malignant melanoma.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Many receptor tyrosine kinase inhibitors have activity on FGF and PDGF receptors that can drive fibroblast function.
“Many of the expanding range of receptor tyrosine kinase inhibitors have some activity on FGF and PDGF receptors that can drive fibroblast function148,149.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [148]
The Discussion section, “Therapeutic targeting of cancer-associated fibroblasts” (page not provided), names three tyrosine kinase inhibitors with activity against PDGF receptors and says imatinib attenuates fibroblast support in mouse models. It discusses inhibiting FGF-2 but does not say these inhibitors act on FGF receptors, so the FGF-receptor part is unsupported. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Tumors: Wounds That Do Not Heal
Flier, J. S., Underhill, L. H., & Dvorak, H. F. (1986) · New England Journal of Medicine · doi:10.1056/nejm198612253152606 · Cited by 4,391 · cited 1× · see citing works
“In addition, in agreement with our studies, and with the notion that the tumor stroma is in many aspects similar to a wound that does not heal (40), an analogous situation was recently described for skin wound healing, during”
ResultOrimo, A., Gupta, P. B., Sgroi, D. C., Arenzana-Seisdedos, F., Delaunay, T., Naeem, R., Carey, V. J., Richardson, A. L., & Weinberg, R. A. (2005) · Cell · doi:10.1016/j.cell.2005.02.034 · Cited by 3,759 · see citing works
Stromal fibroblasts in cancer initiation and progression
Bhowmick, N. A., Neilson, E. G., & Moses, H. L. (2004) · Nature · doi:10.1038/nature03096 · Cited by 2,291 · see citing works
Stromal gene expression predicts clinical outcome in breast cancer
Finak, G., Bertos, N., Pepin, F., Sadekova, S., Souleimanova, M., Zhao, H., Chen, H., Ömeroğlu, G., Meterissian, S. H., Ömeroğlu, A., et al. (2008) · Nature Medicine · doi:10.1038/nm1764 · Cited by 1,687 · see citing works
Molecular characterization of the tumor microenvironment in breast cancer
Allinen, M., Beroukhim, R., Cai, L., Brennan, C., Lahti-Domenici, J., Huang, H., Porter, D., Hu, M., Chin, L., Richardson, A., et al. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.06.010 · Cited by 1,299 · see citing works
Tumor Induction of VEGF Promoter Activity in Stromal Cells
Fukumura, D., Xavier, R., Sugiura, T., Chen, Y., Park, E.-C., Lu, N., Selig, M., Nielsen, G., Taksir, T., Jain, R. K., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81731-6 · Cited by 996 · see citing works
Stromal Fibroblasts in Cancer: A Novel Tumor-Promoting Cell Type
Orimo, A., & Weinberg, R. A. (2006) · Cell Cycle · doi:10.4161/cc.5.15.3112 · Cited by 798 · see citing works
Tumor-stroma interactions in pancreatic ductal adenocarcinoma
Mahadevan, D., & Hoff, D. D. V. (2007) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-06-0686 · Cited by 602 · see citing works
Therapeutic targeting of the tumor microenvironment
Joyce, J. A. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.05.024 · Cited by 580 · see citing works
The stroma reaction myofibroblast: a key player in the control of tumor cell behavior
Desmoulière, A., Guyot, C., & Gabbiani, G. (2004) · The International Journal of Developmental Biology · doi:10.1387/ijdb.041802ad · Cited by 551 · see citing works
Song, S., Ewald, A. J., Stallcup, W. B., Werb, Z., & Bergers, G. (2005) · Nature Cell Biology · doi:10.1038/ncb1288 · Cited by 551 · see citing works
REACTIVE STROMA IN PROSTATE CANCER PROGRESSION
Tuxhorn, J. A., Ayala, G. E., & Rowley, D. R. (2001) · The Journal of Urology · doi:10.1016/s0022-5347(05)65620-0 · Cited by 506 · see citing works
Mesenchymal Stem Cell Features of Ewing Tumors
Tirode, F., Laud-Duval, K., Prieur, A., Delorme, B., Charbord, P., & Delattre, O. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.02.027 · Cited by 506 · see citing works
PDGF receptors as cancer drug targets
Pietras, K., Sjöblom, T., Rubin, K., Heldin, C., & Östman, A. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00089-8 · Cited by 467 · see citing works
Self-citationPietras, K., Pahler, J. C., Bergers, G., & Hanahan, D. (2008) · PLoS Medicine · doi:10.1371/journal.pmed.0050019 · Cited by 452 · see citing works
Self-citationEvolutionary Divergence of Platelet-Derived Growth Factor Alpha Receptor Signaling Mechanisms
Hamilton, T., Klinghoffer, R. A., Corrin, P. D., & Soriano, P. M. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.11.4013-4025.2003 · Cited by 435 · see citing works
Systemic Endocrine Instigation of Indolent Tumor Growth Requires Osteopontin
McAllister, S. S., Gifford, A. M., Greiner, A. L., Kelleher, S. P., Saelzler, M. P., Ince, T. A., Reinhardt, F., Harris, L. N., Hylander, B. L., Repasky, E. A., et al. (2008) · Cell · doi:10.1016/j.cell.2008.04.045 · Cited by 431 · see citing works
Genes that Distinguish Physiological and Pathological Angiogenesis
Seaman, S., Stevens, J., Yang, M., Logsdon, D. L., Graff‐Cherry, C., & Croix, B. S. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.04.017 · Cited by 415 · see citing works
Moinfar, F., Man, Y., Arnould, L., Bratthauer, G. L., Ratschek, M., & Tavassoli, F. A. (2000) · PubMed · Cited by 402 · see citing works
Platelet-derived growth factor C induces liver fibrosis, steatosis, and hepatocellular carcinoma
Campbell, J. S., Hughes, S. D., Gilbertson, D. G., Palmer, T. E., Holdren, M. S., Haran, A. C., Odell, M. M., Bauer, R. L., Ren, H.-P., Haugen, H. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409722102 · Cited by 333 · see citing works
VEGF‐null cells require PDGFR α signaling‐mediated stromal fibroblast recruitment for tumorigenesis
Dong, J., Grunstein, J., Tejada, M. L., Peale, F., Frantz, G. D., Liang, W., Bai, W., Yu, L., Kowalski, J., Liang, X., et al. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600289 · Cited by 294 · see citing works
Mori, R., Shaw, T. J., & Martin, P. B. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20071412 · Cited by 294 · see citing works
Wound healing: The role of growth factors
Grazul‐Bilska, A. T., Johnson, M. L., Bilski, J. J., Redmer, D. A., Reynolds, L. P., Abdullah, A., & Abdullah, K. M. (2003) · Drugs of today · doi:10.1358/dot.2003.39.10.799472 · Cited by 255 · see citing works
Lack of clinical efficacy of imatinib in metastatic melanoma
Ugurel, S., Hildenbrand, R., Zimpfer, A., Rosée, P. G. L., Paschka, P., Sucker, A., Keikavoussi, P., Becker, J. C., Rittgen, W., Hochhaus, A., et al. (2005) · British Journal of Cancer · doi:10.1038/sj.bjc.6602529 · Cited by 243 · see citing works
Forsberg, K., Valyi-Nagy, I. T., Heldin, C., Herlyn, M., & Westermark, B. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.2.393 · Cited by 238 · see citing works
Jaeger, J. C., Koczan, D., Thiesen, H., Ibrahim, S. M., Gross, G., Spang, R., & Kunz, M. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-1820 · Cited by 232 · see citing works
Tumorigenic conversion of immortal human keratinocytes through stromal cell activation
Skobe, M., & Fusenig, N. E. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.3.1050 · Cited by 231 · see citing works
Human breast carcinoma desmoplasia is PDGF initiated
Shao, Z., Nguyen, M. T. N., & Barsky, S. H. (2000) · Oncogene · doi:10.1038/sj.onc.1203785 · Cited by 222 · see citing works
Furuhashi, M., Sjöblom, T., Abramsson, A., Ellingsen, J., Micke, P., Li, H., Folestad, E. B., Eriksson, U., Heuchel, R. L., Betsholtz, C., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-1489 · Cited by 204 · see citing works
Self-citationTissue plasminogen activator is a potent activator of PDGF‐CC
Fredriksson, L., Li, H., Fieber, C., Li, X., & Eriksson, U. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600397 · Cited by 193 · see citing works
Self-citationThe complexities of breast cancer desmoplasia
Walker, R. A. (2001) · Breast Cancer Research · doi:10.1186/bcr287 · Cited by 190 · see citing works
Mesenchymal Stem Cells in Cancer: Tumor-Associated Fibroblasts and Cell-Based Delivery Vehicles
Hall, B., Dembinski, J., Sasser, A., Studeny, M., Andreeff, M., & Marini, F. (2007) · International Journal of Hematology · doi:10.1532/ijh97.06230 · Cited by 171 · see citing works
Exploring the tumour environment: cancer-associated fibroblasts as targets in cancer therapy
Micke, P., & Östman, A. (2005) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.9.6.1217 · Cited by 162 · see citing works
PDGF-D is a potent transforming and angiogenic growth factor
Li, H., Fredriksson, L., Li, X., & Eriksson, U. (2003) · Oncogene · doi:10.1038/sj.onc.1206223 · Cited by 155 · see citing works
Self-citationPontén, A., Li, X., Thorén, P., Aase, K., Sjöblom, T., Östman, A., & Eriksson, U. (2003) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63694-2 · Cited by 154 · see citing works
Self-citationPlatelet-derived growth factor receptor (PDGFR): A target for anticancer therapeutics
R BOARD, & Jayson, G. C. (2005) · Drug Resistance Updates · doi:10.1016/j.drup.2005.03.004 · Cited by 146 · see citing works
Evidence for Nonautonomous Effect of <i>p53</i> Tumor Suppressor in Carcinogenesis
Kiaris, H., Chatzistamou, I., Trimis, G., Frangou-Plemmenou, M., Pafiti-Kondi, A., & Kalofoutis, A. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-3791 · Cited by 128 · see citing works
Tejada, M. L., Yu, L., Dong, J., Jung, K., Meng, G., Peale, F. V., Jr., Frantz, G. D., Hall, L., Liang, X., Gerber, H., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-1770 · Cited by 127 · see citing works
Osteopontin (Eta-1) and Fibroblast Growth Factor-2 Cross-Talk in Angiogenesis
Leali, D., Dell’Era, P., Stabile, H., Sennino, B., Chambers, A. F., Naldini, A., Sozzani, S., Nico, B., Ribatti, D., & Presta, M. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.2.1085 · Cited by 126 · see citing works
PDGF-C Is a Proinflammatory Cytokine that Mediates Renal Interstitial Fibrosis
Eitner, F., Diaeresis]cher, E. B., van Roeyen, C. R. C., Kunter, U., Rong, S., Seikrit, C., Villa, L., Boor, P., Fredriksson, L., Diaeresism, G. B. D., et al. (2008) · Journal of the American Society of Nephrology · doi:10.1681/asn.2007030290 · Cited by 124 · see citing works
Self-citationYoo, K. H., Thornhill, B. A., Forbes, M. S., Coleman, C. M., Marcinko, E. S., Liaw, L., & Chevalier, R. L. (2006) · Kidney International · doi:10.1038/sj.ki.5000357 · Cited by 98 · see citing works
Osteopontin is required for full expression of the transformed phenotype by the ras oncogene
Wu, Y., Denhardt, D. T., & Rittling, S. R. (2000) · British Journal of Cancer · doi:10.1054/bjoc.2000.1200 · Cited by 92 · see citing works
Angiogenesis gene expression profiling in xenograft models to study cellular interactions
Thijssen, V. L., Brandwijk, R. J. M. G. E., Dings, R. P. M., & Griffioen, A. W. (2004) · Experimental Cell Research · doi:10.1016/j.yexcr.2004.06.014 · Cited by 91 · see citing works
PDGFR‐α signaling is critical for tooth cusp and palate morphogenesis
Xu, X., Bringas, P., Soriano, P. M., & Chai, Y. (2004) · Developmental Dynamics · doi:10.1002/dvdy.20197 · Cited by 90 · see citing works
Ball, S. G., Shuttleworth, C. A., & Kielty, C. M. (2006) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2006.09.005 · Cited by 63 · see citing works
Osteopontin: an emerging therapeutic target for anticancer therapy
Jain, S., Chakraborty, G., Bulbule, A., Kaur, R., & Kundu, G. C. (2006) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.11.1.81 · Cited by 49 · see citing works
Johnson, F. M., Krug, L. M., Tran, H. T., Shoaf, S., Prieto, V. G., Tamboli, P., Peeples, B. O., Patel, J. D., & Glisson, B. S. (2005) · Cancer · doi:10.1002/cncr.21640 · Cited by 48 · see citing works
Campbell, J. S., Johnson, M. M., Bauer, R. L., Hudkins, K. L., Gilbertson, D. G., Riehle, K. J., Yeh, M. M., Alpers, C. E., & Fausto, N. (2007) · Differentiation · doi:10.1111/j.1432-0436.2007.00235.x · Cited by 41 · see citing works
Lin, A., Rini, B. I., Derynck, M. K., WEINBERG, V. K., Park, M. M., Ryan, C. J., Rosenberg, J. E., Bubley, G. J., & Small, E. J. (2007) · Clinical Genitourinary Cancer · doi:10.3816/cgc.2007.n.011 · Cited by 32 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
A framework for advancing our understanding of cancer-associated fibroblasts
Sahai, E., Astsaturov, I., Cukierman, E., DeNardo, D. G., Egeblad, M., Evans, R. M., Fearon, D., Greten, F. R., Hingorani, S. R., Hunter, T., et al. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-019-0238-1 · Cited by 3,863 · see citing works
Tumor microenvironment as a therapeutic target in cancer
Xiao, Y. Q., & Yu, D. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107753 · Cited by 1,977 · see citing works
Microenvironmental regulation of tumour angiogenesis
De Palma, M., Biziato, D., & Petrova, T. V. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.51 · Cited by 1,847 · see citing works
Erez, N., Truitt, M., Olson, P., & Hanahan, D. (2010) · Cancer Cell · doi:10.1016/j.ccr.2009.12.041 · Cited by 1,515 · see citing works
Diversity and biology of cancer-associated fibroblasts
Biffi, G., & Tuveson, D. A. (2021) · Physiological Reviews · doi:10.1152/physrev.00048.2019 · Cited by 1,265 · see citing works
Hallmarks of cancer: Interactions with the tumor stroma
Pietras, K., & Östman, A. (2010) · Experimental Cell Research · doi:10.1016/j.yexcr.2010.02.045 · Cited by 1,137 · see citing works
Self-citationTargeting the tumour vasculature: insights from physiological angiogenesis
Chung, A. S., Lee, J., & Ferrara, N. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2868 · Cited by 745 · see citing works
The angiogenic switch in carcinogenesis
Baeriswyl, V., & Christofori, G. (2009) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2009.05.003 · Cited by 624 · see citing works
Cancer-associated fibroblasts in gastrointestinal cancer
Kobayashi, H., Enomoto, A., Woods, S. L., Burt, A. D., Takahashi, M., & Worthley, D. L. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0115-0 · Cited by 596 · see citing works
Cancer-associated fibroblasts and tumor growth – bystanders turning into key players
Östman, A., & Augsten, M. (2009) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2009.01.003 · Cited by 542 · see citing works
Targeting the PDGF signaling pathway in tumor treatment
Heldin, C. (2013) · Cell Communication and Signaling · doi:10.1186/1478-811x-11-97 · Cited by 541 · see citing works
A peek into cancer-associated fibroblasts: origins, functions and translational impact
LeBleu, V. S., & Kalluri, R. (2018) · Disease Models & Mechanisms · doi:10.1242/dmm.029447 · Cited by 539 · see citing works
Improving drug delivery to solid tumors: Priming the tumor microenvironment
Khawar, I. A., Kim, J. H., & Kuh, H.-J. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.12.018 · Cited by 533 · see citing works
Triple‑negative breast cancer therapy: Current and future perspectives (Review)
Won, K., & Spruck, C. (2020) · International Journal of Oncology · doi:10.3892/ijo.2020.5135 · Cited by 532 · see citing works
Fibroblasts in cancer: Unity in heterogeneity
Chhabra, Y., & Weeraratna, A. T. (2023) · Cell · doi:10.1016/j.cell.2023.03.016 · Cited by 488 · see citing works
Liao, D., Luo, Y., Markowitz, D., Xiang, R., & Reisfeld, R. A. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007965 · Cited by 437 · see citing works
Cancer-Associated Fibroblasts as Another Polarized Cell Type of the Tumor Microenvironment
Augsten, M. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00062 · Cited by 427 · see citing works
Spatial Heterogeneity in the Tumor Microenvironment
Yuan, Y. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026583 · Cited by 342 · see citing works
Bu, L., Baba, H., Yoshida, N., Miyake, K., Yasuda, T., Uchihara, T., Tan, P. B. O., & Ishimoto, T. (2019) · Oncogene · doi:10.1038/s41388-019-0765-y · Cited by 324 · see citing works
Tumor-Host Interactions: A Far-Reaching Relationship
McAllister, S. S., & Weinberg, R. A. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.28.4257 · Cited by 326 · see citing works
Pathways mediating VEGF-independent tumor angiogenesis
Ferrara, N. (2009) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2009.11.003 · Cited by 310 · see citing works
Bone marrow–derived fibroblasts are a functionally distinct stromal cell population in breast cancer
Raz, Y., Cohen, N., Shani, O., Bell, R. E., Novitskiy, S. V., Abramovitz, L., Levy, C., Milyavsky, M., Leider–Trejo, L., Moses, H. L., et al. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20180818 · Cited by 270 · see citing works
Paulsson, J., Sjöblom, T., Micke, P., Pontén, F., Landberg, G., Heldin, C., Bergh, J. C. S., Brennan, D. J., Jirström, K., & Östman, A. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.081030 · Cited by 267 · see citing works
Fibroblasts as architects of cancer pathogenesis
Marsh, T., Pietras, K., & McAllister, S. S. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.10.013 · Cited by 263 · see citing works
Self-citationKlinkhammer, B. M., Floege, J., & Boor, P. (2017) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2017.11.008 · Cited by 230 · see citing works
Weber, C., Kothari, A. N., Wai, P. Y., Li, N. Y., Driver, J., Zapf, M. A. C., Franzen, C. A., Gupta, G. N., Osipo, C., Zlobin, A., et al. (2014) · Oncogene · doi:10.1038/onc.2014.410 · Cited by 228 · see citing works
The evolving relationship of wound healing and tumor stroma.
Foster, D. S., Jones, R. E., Ransom, R. C., Longaker, M., & Norton, J. A. (2018) · JCI Insight · doi:10.1172/jci.insight.99911 · Cited by 202 · see citing works
Elkabets, M., Gifford, A. M., Scheel, C., Nilsson, B., Reinhardt, F., Bray, M.-A., Carpenter, A. E., Jirström, K., Magnusson, K., Ebert, B. L., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci43757 · Cited by 201 · see citing works
Role of the metastasis‐promoting protein osteopontin in the tumour microenvironment
Anborgh, P. H., Mutrie, J. C., Tuck, A. B., & Chambers, A. F. (2010) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2010.01115.x · Cited by 199 · see citing works
Tumor stroma as targets for cancer therapy
Zhang, J., & Liu, J. (2012) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.10.003 · Cited by 185 · see citing works
Verginadis, I. I., Avgousti, H., Monslow, J., Skoufos, G., Chinga, F., Kim, K., Leli, N. M., Karagounis, I. V., Bell, B. I., Velalopoulou, A. P., et al. (2022) · Nature Cell Biology · doi:10.1038/s41556-022-00918-8 · Cited by 189 · see citing works
STC1 Expression By Cancer-Associated Fibroblasts Drives Metastasis of Colorectal Cancer
Peña, C., Céspedes, M. V., Lindh, M. B., Kiflemariam, S., Mezheyeuski, A., Edqvist, P.-H. D., Hägglöf, C., Birgisson, H., Bojmar, L., Jirström, K., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-1875 · Cited by 182 · see citing works
Involvement of platelet‐derived growth factor ligands and receptors in tumorigenesis
Heldin, C. ‐., Lennartsson, J., & Westermark, B. (2018) · Journal of Internal Medicine · doi:10.1111/joim.12690 · Cited by 181 · see citing works
Sharon, Y., Raz, Y., Cohen, N., Ben‐Shmuel, A., Doron, H., Geiger, T., & Erez, N. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-1990 · Cited by 177 · see citing works
Qin, X., Yan, M., Wang, X., Xu, Q., Wang, X., Zhu, X., Shi, J., Li, Z., Zhang, J., & Chen, W. (2018) · Theranostics · doi:10.7150/thno.22182 · Cited by 173 · see citing works
Carcinoma-Associated Fibroblasts Are a Promising Therapeutic Target
Togo, S., Polanska, U. M., Horimoto, Y., & Orimo, A. (2013) · Cancers · doi:10.3390/cancers5010149 · Cited by 156 · see citing works
Angiogenesis and the Tumor Microenvironment: Vascular Endothelial Growth Factor and Beyond
Mittal, K., Ebos, J. M. L., & Rini, B. I. (2014) · Seminars in Oncology · doi:10.1053/j.seminoncol.2014.02.007 · Cited by 150 · see citing works
Roswall, P., Bocci, M., Bartoschek, M., Li, H., Kristiansen, G., Jansson, S., Lehn, S., Sjölund, J., Reid, S., Larsson, C., et al. (2018) · Nature Medicine · doi:10.1038/nm.4494 · Cited by 150 · see citing works
Self-citationCancer-associated fibroblasts: how do they contribute to metastasis?
Kwa, M. Q., Herum, K. M., & Brakebusch, C. (2019) · Clinical & Experimental Metastasis · doi:10.1007/s10585-019-09959-0 · Cited by 144 · see citing works
Tumor and stromal pathways mediating refractoriness/resistance to anti-angiogenic therapies
Crawford, Y., & Ferrara, N. (2009) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2009.09.004 · Cited by 140 · see citing works
Ding, W., Knox, T. R., Tschumper, R. C., Wu, W., Schwager, S. M., Boysen, J. C., Jelinek, D. F., & Kay, N. E. (2010) · Blood · doi:10.1182/blood-2010-02-269894 · Cited by 142 · see citing works
Kesavan, K. P., Ratliff, J., Johnson, E. W., Dahlberg, W. K., Asara, J. M., Misra, P., Frangioni, J. V., & Jacoby, D. B. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.066092 · Cited by 138 · see citing works
Moncsek, A., Al‐Suraih, M. S., Trussoni, C. E., O'Hara, S. P., Splinter, P. L., Zuber, C., Patsenker, E., Valli, P. V., Fingas, C. D., Weber, A., et al. (2018) · Hepatology · doi:10.1002/hep.29464 · Cited by 136 · see citing works
The Role of PDGFs and PDGFRs in Colorectal Cancer
Manzat-Saplacan, R. M., Bălăcescu, L., Gherman, C. D., Chira, R. I., Anca, C., Mircea, P. A., Lisencu, C. I., & Bălăcescu, O. (2017) · Mediators of Inflammation · doi:10.1155/2017/4708076 · Cited by 133 · see citing works
Liang, D., Meyer, L. A., Chang, D. W., Lin, J. M., Pu, X., Ye, Y., Gu, J. H., Wu, X., & Lu, K. H. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-0130 · Cited by 132 · see citing works
MiR-21: an environmental driver of malignant melanoma?
Melnik, B. C. (2015) · Journal of Translational Medicine · doi:10.1186/s12967-015-0570-5 · Cited by 129 · see citing works
PDGF-C and PDGF-D signaling in vascular diseases and animal models
Folestad, E. B., Kunath, A., & Wågsäter, D. (2018) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2018.01.005 · Cited by 123 · see citing works
Akt–Girdin Signaling in Cancer-Associated Fibroblasts Contributes to Tumor Progression
Yamamura, Y., Asai, N., Enomoto, A., Kato, T., Mii, S., Kondo, Y., Ushida, K., Niimi, K., Tsunoda, N., Nagino, M., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-1317 · Cited by 121 · see citing works
di Tomaso, E., London, N. R., Fuja, D. G., Logie, J. J., Tyrrell, J. A., Kamoun, W. S., Munn, L. L., & Jain, R. K. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005123 · Cited by 116 · see citing works
Origin and function of tumor stroma fibroblasts
Xouri, G., & Christian, S. (2009) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2009.11.017 · Cited by 116 · see citing works
Naito, Y., Yamamoto, Y., Sakamoto, N., Shimomura, I., Kogure, A., Kumazaki, M., Yokoi, A., Yashiro, M., Kiyono, T., Yanagihara, K., et al. (2019) · Oncogene · doi:10.1038/s41388-019-0832-4 · Cited by 112 · see citing works
Noskovičová, N., Petřek, M., Eickelberg, O., & Heinzelmann, K. (2014) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2014-0294tr · Cited by 111 · see citing works
Functional subsets of mesenchymal cell types in the tumor microenvironment
Cortez, E., Roswall, P., & Pietras, K. (2014) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2013.12.010 · Cited by 107 · see citing works
Self-citationp53 Status in Stromal Fibroblasts Modulates Tumor Growth in an SDF1-Dependent Manner
Addadi, Y., Moskovits, N. B.-C., Granot, D., Lozano, G., Carmi, Y., Apte, R. N., Neeman, M., & Oren, M. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-1146 · Cited by 108 · see citing works
Angiogenesis and expression of PDGF ‐ C , VEGF , CD 105 and HIF ‐1α in human glioblastoma
Clara, C., Marie, S. K. N., Almeida, J. R. W., Wakamatsu, A., Oba‐Shinjo, S. M., Uno, M., Neville, M. A., & Rosemberg, S. (2014) · Neuropathology · doi:10.1111/neup.12111 · Cited by 106 · see citing works
Metabolic exchanges within tumor microenvironment
Chiarugi, P., & Cirri, P. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.10.027 · Cited by 103 · see citing works
Li, M., Li, M., Yin, T., Shi, H., WEN, Y., Zhang, B., Chen, M., Xu, G., Ren, K., & Wei, Y. (2016) · Molecular Medicine Reports · doi:10.3892/mmr.2016.4868 · Cited by 103 · see citing works
The Matrix Revolution: Matricellular Proteins and Restructuring of the Cancer Microenvironment
Gerarduzzi, C., Hartmann, U., Leask, A., & Drobetsky, E. A. (2020) · Cancer Research · doi:10.1158/0008-5472.can-18-2098 · Cited by 96 · see citing works
PDGF Receptors in Tumor Biology: Prognostic and Predictive Potential
Paulsson, J., Ehnman, M., & Östman, A. (2014) · Future Oncology · doi:10.2217/fon.14.83 · Cited by 96 · see citing works
Neuroendocrine tumors and fibrosis: An unsolved mystery?
Laskaratos, F., Rombouts, K., Caplin, M. E., Toumpanakis, C., Thirlwell, C., & Mandair, D. (2017) · Cancer · doi:10.1002/cncr.31079 · Cited by 97 · see citing works
Wang, Y., Tu, K., Liu, D., Guo, L., Chen, Y., Li, Q., Maiers, J. L., Liu, Z., Shah, V. H., Dou, C., et al. (2019) · Hepatology · doi:10.1002/hep.30668 · Cited by 95 · see citing works
Forkhead Box F1 Regulates Tumor-Promoting Properties of Cancer-Associated Fibroblasts in Lung Cancer
Saito, R.-A., Micke, P., Paulsson, J., Augsten, M., Peña, C., Jönsson, P., Botling, J., Edlund, K., Johansson, L., Carlsson, P., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-3644 · Cited by 93 · see citing works
Östman, A. (2017) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2017.09.022 · Cited by 90 · see citing works
Turrell, F. K., Orha, R., Guppy, N., Gillespie, A., Guelbert, M., Starling, C., Haider, S. A., & Isacke, C. M. (2023) · Nature Cancer · doi:10.1038/s43018-023-00525-y · Cited by 90 · see citing works
Jansson, S., Aaltonen, K. E., Bendahl, P., Falck, A., Karlsson, M. E., Pietras, K., & Rydén, L. (2018) · Breast Cancer Research and Treatment · doi:10.1007/s10549-018-4664-7 · Cited by 88 · see citing works
Self-citationAdipose tissue-derived progenitor cells and cancer
Zhang, Y. (2010) · World Journal of Stem Cells · doi:10.4252/wjsc.v2.i5.103 · Cited by 87 · see citing works
Role of miRNAs in Melanoma Metastasis
Gajos-Michniewicz, A., & Czyż, M. (2019) · Cancers · doi:10.3390/cancers11030326 · Cited by 87 · see citing works
Hou, X., Kumar, A., Lee, C., Wang, B., Arjunan, P., Dong, L., Maminishkis, A., Tang, Z., Yang, L., Zhang, F., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1004143107 · Cited by 82 · see citing works
Self-citationThe emerging roles of exosomes in tumor–stroma interaction
Fu, H.-L., Yang, H., Zhang, X., & Xu, W.-R. (2016) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-016-2145-0 · Cited by 77 · see citing works
Cancer-Stromal Cell Interaction and Tumor Angiogenesis in Gastric Cancer
Kitadai, Y. (2009) · Cancer Microenvironment · doi:10.1007/s12307-009-0032-9 · Cited by 76 · see citing works
Novel hepatocellular carcinoma molecules with prognostic and therapeutic potentials
Scaggiante, B. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i5.1268 · Cited by 75 · see citing works
VEGF-independent angiogenic pathways induced by PDGF-C
Li, X., Kumar, A., Zhang, F., Lee, C., Li, Y., Tang, Z., & Arjunan, P. (2010) · Oncotarget · doi:10.18632/oncotarget.141 · Cited by 74 · see citing works
Self-citationJena, B. C., Das, C. K., Bharadwaj, D., & Mandal, M. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188416 · Cited by 70 · see citing works
Wright, J. H., Johnson, M. M., Shimizu‐Albergine, M., Bauer, R. L., Hayes, B. J., Surapisitchat, J., Hudkins, K. L., Riehle, K. J., Johnson, S. C., Yeh, M. M., et al. (2013) · International Journal of Cancer · doi:10.1002/ijc.28421 · Cited by 68 · see citing works
Cordani, M., Pacchiana, R., Butera, G., D’Orazi, G., Scarpa, A., & Donadelli, M. (2016) · Cancer Letters · doi:10.1016/j.canlet.2016.03.046 · Cited by 68 · see citing works
Dzobo, K., & Dandara, C. (2020) · OMICS A Journal of Integrative Biology · doi:10.1089/omi.2020.0023 · Cited by 65 · see citing works
The Association of Serum IL-33 and sST2 with Breast Cancer
Yang, Z., Ling, D.-Y., Xie, Y., Wu, W., Li, J.-R., Jiang, J. F., Zheng, J.-L., Fan, Y., & Zhang, Y. (2015) · Disease Markers · doi:10.1155/2015/516895 · Cited by 64 · see citing works
The fibroblast Tiam1-osteopontin pathway modulates breast cancer invasion and metastasis
Xu, K., Tian, X., Oh, S. Y., Movassaghi, M., Naber, S. P., Kuperwasser, C., & Buchsbaum, R. J. (2016) · Breast Cancer Research · doi:10.1186/s13058-016-0674-8 · Cited by 64 · see citing works
Tsioumpekou, M., Cunha, S. I., Ma, H., Åhgren, A., Cedervall, J., Olsson, A., Heldin, C., & Lennartsson, J. (2019) · Theranostics · doi:10.7150/thno.37851 · Cited by 64 · see citing works
Yu, S., Wang, S., Wang, X., & Xu, X. (2024) · Cancer Cell International · doi:10.1186/s12935-024-03518-8 · Cited by 65 · see citing works
Shah, G., Loizos, N., Youssoufian, H., Schwartz, J. D., & Rowinsky, E. K. (2010) · Cancer · doi:10.1002/cncr.24788 · Cited by 62 · see citing works
Clinico-pathological and biological prognostic variables in squamous cell carcinoma of the vulva
Gadducci, A., Tana, R., Barsotti, C., Guerrieri, M. E., & Genazzani, A. R. (2011) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2011.09.003 · Cited by 62 · see citing works
Kono, S. A., Heasley, L. E., Doebele, R. C., & Camidge, D. R. (2012) · Current Cancer Drug Targets · doi:10.2174/156800912799095144 · Cited by 59 · see citing works
Computational pathology: Exploring the spatial dimension of tumor ecology
Nawaz, S., & Yuan, Y. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.11.018 · Cited by 59 · see citing works
Mezawa, Y., & Orimo, A. (2021) · FEBS Journal · doi:10.1111/febs.15851 · Cited by 59 · see citing works
Significance of myofibroblasts in oral squamous cell carcinoma
Thode, C., Jørgensen, T. G., Dabelsteen, E., Mackenzie, I. C., & Dabelsteen, S. (2011) · Journal of Oral Pathology and Medicine · doi:10.1111/j.1600-0714.2010.00999.x · Cited by 57 · see citing works
Yoon, H., Tang, C.-M., Banerjee, S., Yebra, M., Noh, S., Burgoyne, A. M., la Torre, J. D., Siena, M. D., Liu, M., Klug, L. R., et al. (2021) · Oncogene · doi:10.1038/s41388-021-01685-w · Cited by 56 · see citing works
ADAM12 Produced by Tumor Cells Rather than Stromal Cells Accelerates Breast Tumor Progression
Fröhlich, C., Nehammer, C., Albrechtsen, R., Kronqvist, P., Kveiborg, M., Sehara‐Fujisawa, A., Mercurio, A. M., & Wewer, U. M. (2011) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-11-0100 · Cited by 56 · see citing works
Tenascin-C, a Prognostic Determinant of Esophageal Squamous Cell Carcinoma
Yang, Z., Yeo, S.-Y., Yin, Y.-X., Lin, Z., Lee, H., Xuan, Y., Cui, Y. R., & Kim, S. (2016) · PLoS ONE · doi:10.1371/journal.pone.0145807 · Cited by 55 · see citing works
Kim, K., Jung, J., Yoo, H. J., Hyun, J., Park, J., Na, D., & Yeon, J. H. (2020) · Journal of Functional Biomaterials · doi:10.3390/jfb11030049 · Cited by 54 · see citing works
Gao, D., Fang, L., Liu, C., Yang, M., Yu, X., Wang, L., Zhang, W., Sun, C., & Zhuang, J. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115622 · Cited by 53 · see citing works
Platelet CLEC2-Podoplanin Axis as a Promising Target for Oral Cancer Treatment
Hwang, B.-O., Park, S.-Y., Cho, E. S., Zhang, X., Lee, S., Ahn, H., Chun, K., Chung, W., & Song, N. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.807600 · Cited by 52 · see citing works
Angiogenesis and targeted therapy in the tumour microenvironment: From basic to clinical practice
Yang, S., Fang, Y., Ma, Y., Wang, F., Wang, Y., Jia, J., Yang, Y., Sun, W., Zhou, Q., & Li, Z. (2025) · Clinical and Translational Medicine · doi:10.1002/ctm2.70313 · Cited by 56 · see citing works
Alsibai, K. D., & Meseure, D. (2017) · Developmental Dynamics · doi:10.1002/dvdy.24548 · Cited by 51 · see citing works
Peng, C., Zou, X., Xia, W., Gao, H., Li, Z., Liu, N., Xu, Z., Gao, C., He, Z., Niu, W., et al. (2018) · Bioscience Reports · doi:10.1042/bsr20180243 · Cited by 52 · see citing works
Co-migration of colon cancer cells and CAFs induced by TGFβ₁ enhances liver metastasis
Gonzalez-Zubeldia, I., Dotor, J., Redrado, M., Bleau, A.-M., Manrique, I., de Aberasturi, A. L., Villalba, M., & Calvo, A. (2015) · Cell and Tissue Research · doi:10.1007/s00441-014-2075-6 · Cited by 51 · see citing works
Hurst, N. J., Najy, A. J., Ustach, C. V., Movilla, L. S., & Kim, H.-R. C. (2011) · Biochemical Journal · doi:10.1042/bj20111020 · Cited by 51 · see citing works
Analysis of the paracrine loop between cancer cells and fibroblasts using a microfluidic chip
Hsu, T., Xiao, J., Tsao, Y.-W., Kao, Y.-L., Huang, S., Liao, W., & Lee, C. (2011) · Lab on a Chip · doi:10.1039/c1lc20090a · Cited by 51 · see citing works
Impact of mesenchymal stem cells’ secretome on glioblastoma pathophysiology
de Castro, J. V., Gomes, E. D., Granja, S., Anjo, S. I., Baltazar, F., Manadas, B. J., Salgado, A. J., & Costa, B. M. (2017) · Journal of Translational Medicine · doi:10.1186/s12967-017-1303-8 · Cited by 51 · see citing works
Regulation of cancer stem cell activities by tumor-associated macrophages.
Jinushi, M., Baghdadi, M., Chiba, S., & Yoshiyama, H. (2012) · Europe PMC (PubMed Central) · Cited by 49 · see citing works
- Authors
- Anderberg, C., Li, H., Fredriksson, L., Andrae, J., Betsholtz, C., Li, X., Eriksson, U., & Pietras, K.
- Affiliations
- Ludwig Cancer Research (SE)
- 1Ludwig Institute for Cancer Research Ltd., Stockholm Branch, and
- Karolinska Institutet (SE)
- National Institutes of Health (US)
- Venue
- Cancer Research
- Published
- 2008-12-31
- Volume
- 69
- Issue
- 1
- Pages
- 369-378
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC2613547
- OpenAlex
- W2160108544
- Cited by
- 249
- References
- 49
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 6 · 2023: 16 · 2022: 10 · 2021: 10 · 2020: 15 · 2019: 12 · 2018: 19 · 2017: 17 · 2016: 16 · 2015: 21 · 2014: 18 · 2013: 15 · 2012: 12
- FWCI
- 6.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Cancer Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Vanderbilt University
- Cancerfonden
- Karolinska Institutet
- Vetenskapsrådet
- National Institutes of Health (Z99 EY999999)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Keywords
- PDGF-C, paracrine signaling, cancer-associated fibroblasts, tumor microenvironment, tumor stroma, melanoma, PDGF receptor alpha, osteopontin, tumor growth, fibroblast recruitment, stromal support
- MeSH terms
- Animals, Fibroblasts, Humans, Lymphokines, Melanoma, Melanoma, Experimental, Mice, Inbred C57BL, Platelet-Derived Growth Factor, Skin Neoplasms, Signal Transduction, Stromal Cells, Receptor, Platelet-Derived Growth Factor alpha, NIH 3T3 Cells, Cell Line, Tumor, Cell Growth Processes, Mice, Osteopontin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
