Involvement of chemokine receptors in breast cancer metastasis
Abstract
Breast cancer is characterized by a distinct metastatic pattern involving the regional lymph nodes, bone marrow, lung and liver. Tumour cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. Here we report that the chemokine receptors CXCR4 and CCR7 are highly expressed in human breast cancer cells, malignant breast tumours and metastases. Their respective ligands CXCL12/SDF-1alpha and CCL21/6Ckine exhibit peak levels of expression in organs representing the first destinations of breast cancer metastasis. In breast cancer cells, signalling through CXCR4 or CCR7 mediates actin polymerization and pseudopodia formation, and subsequently induces chemotactic and invasive responses. In vivo, neutralizing the interactions of CXCL12/CXCR4 significantly impairs metastasis of breast cancer cells to regional lymph nodes and lung. Malignant melanoma, which has a similar metastatic pattern as breast cancer but also a high incidence of skin metastases, shows high expression levels of CCR10 in addition to CXCR4 and CCR7. Our findings indicate that chemokines and their receptors have a critical role in determining the metastatic destination of tumour cells.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Tumor cell homing to distant sites involves the HIF-regulated chemokine receptor CXCR4, which binds to SDF-1α in secondary organs and drives breast cancer metastasis.
“Tumor cell homing to distant sites involves the HIF-regulated chemokine receptor CXCR4 (Staller et al., 2003), which binds to stromalderived factor-1 (SDF-1α) in secondary organs and drives breast cancer metastasis (Muller et al., 2001).”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Muller et al., 2001
Compared to high CXCL1/2 expression in lung metastatic cell lines, expression of CXCR1, CXCR2 and DARC is negligibly low at RNA and protein levels.
“Compared to the high levels of CXCL1/2 expression in lung metastatic cell lines, the expression of CXCR1, CXCR2 and DARC was negligibly low both at the RNA and protein levels (Figure 2C and Figure S2F and (Muller et al., 2001)).”
From A CXCL1 Paracrine Network Links Cancer Chemoresistance and Metastasis (2012) · cites this paper as Muller et al., 2001
CXCL12 is particularly highly expressed in target organs for breast cancer metastasis.
“and is particularly highly expressed in target organs for breast cancer metastasis50.”
From Inflammation and cancer (2002) · cites this paper as [50]
The chemotactic activity of extracts of organs targeted by breast cancer cells (bone marrow, liver, lung and lymph nodes) can be neutralized by anti-CXCR4 antibodies.
“and the chemotactic activity of extracts of organs targeted by breast cancer cells (bone marrow, liver, lung and lymph nodes) can be neutralized by anti-CXCR4 antibodies.”
From Inflammation and cancer (2002) · cites this paper as [50]
CXCL12 triggers chemotaxis of malignant mammary carcinoma cells in vitro.
“CXCL12 triggers chemotaxis of malignant mammary carcinoma cells in vitro”
From Inflammation and cancer (2002) · cites this paper as [50]
In a mouse model, the pattern of breast cancer metastases is in part governed by specific interactions between CXCR4 and its ligand SDF-1/CXCL12.
“Studies using a mouse model by Muller and colleagues suggest that the pattern of breast cancer metastases is in part governed by specific interactions between CXCR4 and its ligand SDF-1/CXCL12 (ref. 50).”
From Inflammation and cancer (2002) · cites this paper as [50]
Cites
Zlotnik, A., & Yoshie, O. (2000) · Immunity · doi:10.1016/s1074-7613(00)80165-x · Cited by 3,859 · see citing works
Self-citationHolland, P. M., Abramson, R. D., Watson, R., & Gelfand, D. H. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.16.7276 · Cited by 2,694 · see citing works
Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development
Zou, Y.-R., Kottmann, A. H., Kuroda, M., Taniuchi, I., & Littman, D. R. (1998) · Nature · doi:10.1038/31269 · Cited by 2,494 · see citing works
Förster, R., Schubel, A., Breitfeld, D., Kremmer, E., Renner‐Müller, I., Wolf, E., & Lipp, M. (1999) · Cell · doi:10.1016/s0092-8674(00)80059-8 · Cited by 2,348 · see citing works
Beahrs, O. H., & Henson, D. E. (1992) · Medical Entomology and Zoology · Cited by 2,340 · see citing works
Nagasawa, T., Hirota, S., Tachibana, K., Takakura, N., Nishikawa, S.-I., Kitamura, Y., Yoshida, N., Kikutani, H., & Kishimoto, T. (1996) · Nature · doi:10.1038/382635a0 · Cited by 2,338 · see citing works
The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry
Bleul, C. C., Farzan, M., Choe, H., Parolin, C., Clark‐Lewis, I., Sodroski, J., & Springer, T. A. (1996) · Nature · doi:10.1038/382829a0 · Cited by 1,953 · see citing works
Ma, Q., Jones, D., Borghesani, P. R., Segal, R. A., Nagasawa, T., Kishimoto, T., Bronson, R. T., & Springer, T. A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.16.9448 · Cited by 1,683 · see citing works
Dependence of Human Stem Cell Engraftment and Repopulation of NOD/SCID Mice on CXCR4
Peled, A., Petit, I., Kollet, O., Magid, M., Ponomaryov, T., Byk, T., Nagler, A., Ben-Hur, H., Many, A., Shultz, L., et al. (1999) · Science · doi:10.1126/science.283.5403.845 · Cited by 1,644 · see citing works
The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract
Tachibana, K., Hirota, S., Iizasa, H., Yoshida, H., Kawabata, K., Kataoka, Y., Kitamura, Y., Matsushima, K., Yoshida, N., Nishikawa, S.-I., et al. (1998) · Nature · doi:10.1038/31261 · Cited by 1,527 · see citing works
A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1)
Bleul, C. C., Fuhlbrigge, R. C., Casasnovas, J. M., Aiuti, A., & Springer, T. A. (1996) · The Journal of experimental medicine · doi:10.1084/jem.184.3.1101 · Cited by 1,482 · see citing works
Gunn, M. D., Kyuwa, S., Tam‐Amersdorfer, C., Kakiuchi, T., Matsuzawa, A., Williams, L. T., & Nakano, H. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.3.451 · Cited by 1,019 · see citing works
Gunn, M. D., Tangemann, K., Tam‐Amersdorfer, C., Cyster, J. G., Rosen, S. D., & Williams, L. T. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.1.258 · Cited by 1,001 · see citing works
Chemokines and the Arrest of Lymphocytes Rolling Under Flow Conditions
Campbell, J. J., Hedrick, J. A., Zlotnik, A., Siani, M. A., Thompson, D. A., & Butcher, E. C. (1998) · Science · doi:10.1126/science.279.5349.381 · Cited by 994 · see citing works
Self-citationCXC chemokines in angiogenesis
Belperio, J. A., Keane, M. P., Arenberg, D. A., Addison, C., Ehlert, J. E., Burdick, M. D., & Strieter, R. M. (2000) · Journal of Leukocyte Biology · doi:10.1189/jlb.68.1.1 · Cited by 801 · see citing works
Signal Sequence Trap: a Cloning Strategy for Secreted Proteins and Type I Membrane Proteins
Tashiro, K., Tada, H., Heilker, R., Shirozu, M., Nakano, T., & Honjo, T. (1993) · Science · doi:10.1126/science.8342023 · Cited by 712 · see citing works
Lymphocyte Trafficking and Regional Immunity
Butcher, E. C., Williams, M. B., Youngman, K. R., Rott, L. S., & Briskin, M. (1999) · Advances in immunology · doi:10.1016/s0065-2776(08)60022-x · Cited by 673 · see citing works
Chemokines in tissue-specific and microenvironment-specific lymphocyte homing
Campbell, J. J., & Butcher, E. C. (2000) · Current Opinion in Immunology · doi:10.1016/s0952-7915(00)00096-0 · Cited by 625 · see citing works
CTACK, a skin-associated chemokine that preferentially attracts skin-homing memory T cells
Morales, J., Homey, B., Vicari, A. P., Hudak, S. A., Oldham, E. R., Hedrick, J. A., Orozco, R., Copeland, N. G., Jenkins, N. A., McEvoy, L. M., et al. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.25.14470 · Cited by 507 · see citing works
Self-citationBurger, J. A., Burger, M., & Kipps, T. J. (1999) · Blood · doi:10.1182/blood.v94.11.3658 · Cited by 506 · see citing works
Hendrix, C. W., Flexner, C. W., MacFarland, R. T., Giandomenico, C. M., Fuchs, E. J., Redpath, E., Bridger, G. J., & Henson, G. W. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.6.1667-1673.2000 · Cited by 503 · see citing works
Koshiba, T., Hosotani, R., Miyamoto, Y., Ida, J., Tsuji, S., Nakajima, S., Kawaguchi, M., Kobayashi, H., Doi, R., Hori, T., et al. (2000) · PubMed · Cited by 427 · see citing works
Commentary from Westminster. ECT at Broadmoor.
Deitch, R. (1980) · PubMed · Cited by 408 · see citing works
Chemotactic peptide modulation of actin assembly and locomotion in neutrophils.
Howard, T. H., & Meyer, W. H. (1984) · The Journal of Cell Biology · doi:10.1083/jcb.98.4.1265 · Cited by 352 · see citing works
Homey, B., Wang, W., Soto, H., Buchanan, M. E., Wiesenborn, A., Catron, D., Müller, A., McClanahan, T. K., Dieu‐Nosjean, M., Orozco, R., et al. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.7.3465 · Cited by 332 · see citing works
Self-citationChemokines and their role in tumor growth and metastasis
Wang, J. M., Deng, X., Gong, W., & Su, S. (1998) · Journal of Immunological Methods · doi:10.1016/s0022-1759(98)00128-8 · Cited by 308 · see citing works
Luboshits, G., Shina, S., Kaplan, O., Engelberg, S., Nass, D., Lifshitz-Mercer, B., Chaitchik, S., Keydar, I., & Ben‐Baruch, A. (1999) · PubMed · Cited by 297 · see citing works
Vassileva, G., Soto, H., Zlotnik, A., Nakano, H., Kakiuchi, T., Hedrick, J. A., & Lira, S. A. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.190.8.1183 · Cited by 213 · see citing works
Self-citationMöhle, R., Failenschmid, C., Bautz, F., et al. (1999) · Leukemia · doi:10.1038/sj.leu.2401602 · Cited by 185 · see citing works
Identification and characterization of a novel beta chemokine containing six conserved cysteines
Hedrick, J. A., & Zlotnik, A. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.159.4.1589 · Cited by 161 · see citing works
Self-citationAntitumor Effects of the Mouse Chemokine 6Ckine/SLC Through Angiostatic and Immunological Mechanisms
Vicari, A. P., Aït‐Yahia, S., Chemin, K., Müeller, A., Zlotnik, A., & Caux, C. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.4.1992 · Cited by 153 · see citing works
Self-citationMöhle, R., Schittenhelm, M. M., Failenschmid, C., et al. (2000) · British Journal of Haematology · doi:10.1046/j.1365-2141.2000.02157.x · Cited by 146 · see citing works
Hromas, R., Kim, C. H., Klemsz, M., et al. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.159.6.2554 · Cited by 140 · see citing works
Migration of tumor cells to organ-derived chemoattractants.
Hujanen, E., & Terranova, V. P. (1985) · PubMed · Cited by 134 · see citing works
Nicolson, G. L. (1993) · Cancer and Metastasis Reviews · doi:10.1007/bf00665961 · Cited by 130 · see citing works
SAIKI, I., Murata, J., Nakajima, M., et al. (1990) · PubMed · Cited by 116 · see citing works
Molecular Basis of Tumor Progression: Mechanisms of Organ‐Specific Tumor Metastasis
Yeatman, T. J., & Nicolson, G. L. (1993) · Seminars in Surgical Oncology · doi:10.1002/j.1098-2388.1993.tb00018.x · Cited by 89 · see citing works
Stromal cells in lymph nodes attractB‐lymphoma cells via production ofstromal cell‐derived factor‐1
Arai, J. A., Yasukawa, M., Yakushijin, Y., et al. (2000) · European Journal Of Haematology · doi:10.1034/j.1600-0609.2000.90147.x · Cited by 76 · see citing works
PATTERNS OF RECURRENT DISEASE IN BREAST CANCER
Bruce, J., Carter, D. C., & Fraser, J. D. (1970) · The Lancet · doi:10.1016/s0140-6736(70)90829-9 · Cited by 75 · see citing works
Verschueren, H., der Taelen, I. V., Dewit, J., Braekeleer, J. D., & BAETSELIER, P. D. (1994) · Journal of Leukocyte Biology · doi:10.1002/jlb.55.4.552 · Cited by 51 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Coussens, L. M., & Werb, Z. (2002) · Nature · doi:10.1038/nature01322 · Cited by 15,111 · see citing works
Mantovani, A., Allavena, P., Sica, A., & Balkwill, F. (2008) · Nature · doi:10.1038/nature07205 · Cited by 11,399 · see citing works
New functions for the matrix metalloproteinases in cancer progression
Egeblad, M., & Werb, Z. (2002) · Nature Reviews Cancer · doi:10.1038/nrc745 · Cited by 6,108 · see citing works
Tumour exosome integrins determine organotropic metastasis
Hoshino, A., Costa-Silva, B., Shen, T.-L., Rodrigues, G., Hashimoto, A., Tesic Mark, M., Molina, H., Kohsaka, S., Di Giannatale, A., Ceder, S., et al. (2015) · Nature · doi:10.1038/nature15756 · Cited by 5,101 · see citing works
Microenvironmental regulation of metastasis
Joyce, J. A., & Pollard, J. W. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2618 · Cited by 3,684 · see citing works
VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche
Kaplan, R. N., Riba, R. D., Zacharoulis, S., Bramley, A. H., Vincent, L., Costa, C., MacDonald, D. D., Jin, D. K., Shido, K., Kerns, S. A., et al. (2005) · Nature · doi:10.1038/nature04186 · Cited by 3,288 · see citing works
Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1
Ceradini, D. J., Kulkarni, A. R., Callaghan, M. J., Tepper, O. M., Bastidas, N., Kleinman, M. E., Capla, J. M., Galiano, R. D., Levine, J. P., & Gurtner, G. C. (2004) · Nature Medicine · doi:10.1038/nm1075 · Cited by 2,600 · see citing works
Cancer and the chemokine network
Balkwill, F. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1388 · Cited by 2,343 · see citing works
Immunosuppressive networks in the tumour environment and their therapeutic relevance
Zou, W. (2005) · Nature Reviews Cancer · doi:10.1038/nrc1586 · Cited by 2,057 · see citing works
Metastatic colonization by circulating tumour cells
Massagué, J., & Obenauf, A. C. (2016) · Nature · doi:10.1038/nature17038 · Cited by 2,062 · see citing works
Pre-metastatic niches: organ-specific homes for metastases
Peinado, H., Zhang, H., Matei, I. R., Costa-Silva, B., Hoshino, A., Rodrigues, G., Psaila, B., Kaplan, R. N., Bromberg, J. F., Kang, Y., et al. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.6 · Cited by 1,889 · see citing works
Lin, Y., Xu, J., & Lan, H. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0760-3 · Cited by 1,398 · 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
Inflammation and cancer: how hot is the link?
Aggarwal, B. B., Shishodia, S., Sandur, S. K., Pandey, M. K., & Sethi, G. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2006.06.029 · Cited by 1,312 · see citing works
Inflammation and cancer: advances and new agents
Crusz, S. M., & Balkwill, F. R. (2015) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2015.105 · Cited by 1,184 · see citing works
A CXCL1 Paracrine Network Links Cancer Chemoresistance and Metastasis
Acharyya, S., Oskarsson, T., Vanharanta, S., Malladi, S., Kim, J., Morris, P. G., Manova-Todorova, K., Leversha, M., Hogg, N., Seshan, V. E., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.042 · Cited by 1,085 · see citing works
The inflammatory micro-environment in tumor progression: the role of tumor-associated macrophages.
Allavena, P., Sica, A., Solinas, G., Porta, C., & Mantovani, A. (2008) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2007.07.004 · Cited by 1,044 · see citing works
Regulation of cancer cell migration and bone metastasis by RANKL.
Jones, D. H., Nakashima, T., Sanchez, O. H., Kozieradzki, I., Komarova, S. V., Sarosi, I., Morony, S., Rubin, E., Sarao, R., Hojilla, C. V., et al. (2006) · Nature · doi:10.1038/nature04524 · Cited by 796 · see citing works
Hernandez, P. A., Gorlin, R. J., Lukens, J. N., Taniuchi, S., Bohinjec, J., Francois, F., Klotman, M. E., & Diaz, G. A. (2003) · Nature Genetics · doi:10.1038/ng1149 · Cited by 722 · see citing works
Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer
Wigerup, C., Påhlman, S., & Bexell, D. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.04.009 · Cited by 687 · see citing works
“, 2003), which binds to stromalderived factor-1 (SDF-1α) in secondary organs and drives breast cancer metastasis (Muller et al., 2001).”
BackgroundMacrophage polarization in pathology
Sica, A., Erreni, M., Allavena, P., & Porta, C. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-1995-y · Cited by 673 · see citing works
Helbig, G., Christopherson, K. W., Bhat-Nakshatri, P., Kumar, S., Kishimoto, H., Miller, K. D., Broxmeyer, H. E., & Nakshatri, H. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300609200 · Cited by 639 · see citing works
Chen, Q., Zhang, X. H.-F., & Massagué, J. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.08.025 · Cited by 619 · see citing works
Cancer related inflammation: the macrophage connection
Sica, A., Allavena, P., & Mantovani, A. (2008) · Cancer Letters · doi:10.1016/j.canlet.2008.03.028 · Cited by 601 · see citing works
Gjerdrum, C., Tiron, C., Høiby, T., Stefansson, I., Haugen, H., Sandal, T., Collett, K., Li, S., McCormack, E., Gjertsen, B. T., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909333107 · Cited by 594 · see citing works
Role of chemokines in tumor growth
Raman, D., Baugher, P. J., Thu, Y. M., & Richmond, A. (2007) · Cancer Letters · doi:10.1016/j.canlet.2007.05.013 · Cited by 578 · see citing works
A microfluidic 3D in vitro model for specificity of breast cancer metastasis to bone
Bersini, S., Jeon, J. S., Dubini, G., Arrigoni, C., Chung, S., Charest, J. L., Moretti, M., & Kamm, R. D. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2013.11.050 · Cited by 534 · see citing works
A history of exploring cancer in context
Maman, S., & Witz, I. P. (2018) · Nature Reviews Cancer · doi:10.1038/s41568-018-0006-7 · Cited by 502 · see citing works
Metastatic and triple-negative breast cancer: challenges and treatment options
Al-Mahmood, S., Sapiezynski, J., Garbuzenko, O. B., & Minko, T. (2018) · Drug Delivery and Translational Research · doi:10.1007/s13346-018-0551-3 · Cited by 524 · see citing works
Cancer as a robust system: implications for anticancer therapy
Kitano, H. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1300 · Cited by 456 · see citing works
The pre-metastatic niche: finding common ground
Sceneay, J., Smyth, M. J., & Möller, A. (2013) · Cancer and Metastasis Reviews · doi:10.1007/s10555-013-9420-1 · Cited by 422 · see citing works
Self-citationChen, I. X., Chauhan, V. P., Posada, J., Ng, M. R., Wu, M. W., Adstamongkonkul, P., Huang, P., Lindeman, N., Langer, R., & Jain, R. K. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1815515116 · Cited by 406 · see citing works
Chemokines: agents for the immunotherapy of cancer?
Homey, B., Müller, A., & Zlotnik, A. (2002) · Nature Reviews Immunology · doi:10.1038/nri748 · Cited by 398 · see citing works
Self-citationBiological applications of microfluidic gradient devices
Kim, S., Kim, H. J., & Jeon, N. L. (2010) · Integrative Biology · doi:10.1039/c0ib00055h · Cited by 366 · see citing works
Hoshida, T., Isaka, N., Hagendoorn, J., di Tomaso, E., Chen, Y.-L., Pytowski, B., Fukumura, D., Padera, T. P., & Jain, R. K. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-1392 · Cited by 361 · see citing works
Technologies for circulating tumor cell separation from whole blood
Bankó, P., Lee, S. Y., Nagygyörgy, V., Zrínyi, M., Chae, C. H., Cho, D. H., & Telekes, A. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0735-4 · Cited by 358 · see citing works
Vicari, A. P., & Caux, C. (2002) · Cytokine & Growth Factor Reviews · doi:10.1016/s1359-6101(01)00033-8 · Cited by 351 · see citing works
Hepatic stellate cells suppress NK cell-sustained breast cancer dormancy
Correia, A. L., Guimaraes, J. C., Auf der Maur, P., De Silva, D., Trefny, M. P., Okamoto, R., Bruno, S., Schmidt, A., Mertz, K., Volkmann, K., et al. (2021) · Nature · doi:10.1038/s41586-021-03614-z · Cited by 339 · see citing works
Oxidative stress promotes myofibroblast differentiation and tumour spreading
Toullec, A., Gerald, D., Despouy, G., Bourachot, B., Cardon, M., Lefort, S., Richardson, M., Rigaill, G., Parrini, M., Lucchesi, C., et al. (2010) · EMBO Molecular Medicine · doi:10.1002/emmm.201000073 · Cited by 339 · see citing works
Microenvironmental regulation of cancer development
Hu, M., & Polyak, K. (2008) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2007.12.006 · Cited by 330 · see citing works
Yoshie, O., Fujisawa, R., Nakayama, T., Harasawa, H., Tago, H., Izawa, D., Hieshima, K., Tatsumi, Y., Matsushima, K., Hasegawa, H., et al. (2002) · Blood · doi:10.1182/blood.v99.5.1505 · Cited by 326 · see citing works
Microfluidic Endothelium for Studying the Intravascular Adhesion of Metastatic Breast Cancer Cells
Song, J. W., Cavnar, S. P., Walker, A. C., Luker, K. E., Gupta, M., Tung, Y.-C., Luker, G. D., & Takayama, S. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005756 · Cited by 317 · see citing works
Role of hypoxia-inducible factors in breast cancer metastasis
Gilkes, D. M., & Semenza, G. L. (2013) · Future Oncology · doi:10.2217/fon.13.92 · Cited by 274 · see citing works
Fitamant, J., Guenebeaud, C., Coissieux, M.-M., Guix, C., Treilleux, I., Scoazec, J.-Y., Bachelot, T., Bernet, A., & Mehlen, P. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709810105 · Cited by 241 · see citing works
Tumors and inflammatory infiltrates: Friends or foes?
Brigati, C., Noonan, D. M., Albini, A., & Benelli, R. (2002) · Clinical & Experimental Metastasis · doi:10.1023/a:1015587423262 · Cited by 230 · see citing works
Biological and Pharmacological Aspects of the NK1-Receptor
Garcia-Recio, S., & Gascón, P. (2015) · BioMed Research International · doi:10.1155/2015/495704 · Cited by 226 · see citing works
Epigenetic expansion of VHL-HIF signal output drives multiorgan metastasis in renal cancer
Vanharanta, S., Shu, W., Brenet, F., Hakimi, A. A., Heguy, A., Viale, A., Reuter, V. E., Hsieh, J. J.-D., Scandura, J. M., & Massagué, J. (2013) · Nature Medicine · doi:10.1038/nm.3029 · Cited by 215 · see citing works
Kamei, K.-I., Mashimo, Y., Koyama, Y., Fockenberg, C., Nakashima, M., Nakajima, M., Li, J., & Chen, Y. (2015) · Biomedical Microdevices · doi:10.1007/s10544-015-9928-y · Cited by 196 · see citing works
Chemokines as mediators of neovascularization
Keeley, E. C., Mehrad, B., & Strieter, R. M. (2008) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.108.162925 · Cited by 192 · see citing works
CXC chemokines located in the 4q21 region are up-regulated in breast cancer
Bieche, I., Chavey, C., Andrieu, C., Busson, M., Vacher, S., Le Corre, L., Guinebretiere, J.-M., Burlinchon, S., Lidereau, R., & Lazennec, G. (2007) · Endocrine Related Cancer · doi:10.1677/erc.1.01301 · Cited by 183 · see citing works
Targeting Vascular Pericytes in Hypoxic Tumors Increases Lung Metastasis via Angiopoietin-2
Keskin, D., Kim, J., Cooke, V. G., Wu, C.-C., Sugimoto, H., Gu, C., De Palma, M., Kalluri, R., & LeBleu, V. S. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.01.035 · Cited by 165 · see citing works
Cancer Stem Cells and Epithelial-to-Mesenchymal Transition in Cancer Metastasis
Celià-Terrassa, T., & Jolly, M. K. (2020) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a036905 · Cited by 163 · see citing works
Fibroblast-derived CXCL12 promotes breast cancer metastasis by facilitating tumor cell intravasation
Ahirwar, D. K., Nasser, M. W., Ouseph, M. M., Elbaz, M., Cuitiño, M. C., Kladney, R. D., Varikuti, S., Kaul, K., Satoskar, A. R., Ramaswamy, B., et al. (2018) · Oncogene · doi:10.1038/s41388-018-0263-7 · Cited by 162 · see citing works
A review of microfluidic approaches for investigating cancer extravasation during metastasis
Ma, Y.-H. V., Middleton, K., You, L., & Sun, Y. (2018) · Microsystems & Nanoengineering · doi:10.1038/micronano.2017.104 · Cited by 154 · see citing works
A microfluidic-based device for study of transendothelial invasion of tumor aggregates in realtime
Zhang, Q., Liu, T., & Qin, J. (2012) · Lab on a Chip · doi:10.1039/c2lc00030j · Cited by 151 · see citing works
Emerging roles and therapeutic value of exosomes in cancer metastasis
Wu, M., Wang, G., Hu, W., Yao, Y., & Yu, X.-F. (2019) · Molecular Cancer · doi:10.1186/s12943-019-0964-8 · Cited by 140 · see citing works
The role of chemoattraction in cancer metastases
Moore, M. A. S. (2001) · BioEssays · doi:10.1002/bies.1095 · Cited by 138 · see citing works
Targeting hypoxic tumour cells to overcome metastasis
Bennewith, K. L., & Dedhar, S. (2011) · BMC Cancer · doi:10.1186/1471-2407-11-504 · Cited by 109 · see citing works
Soria, G., Yaal-Hahoshen, N., Azenshtein, E., Shina, S., Leider-Trejo, L., Ryvo, L., Cohen-Hillel, E., Shtabsky, A., Ehrlich, M., Meshel, T., et al. (2008) · Cytokine · doi:10.1016/j.cyto.2008.08.002 · Cited by 92 · see citing works
Lavergne, E., Combadière, C., Iga, M., Boissonnas, A., Bonduelle, O., Maho, M., Debré, P., & Combadiere, B. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.6.3755 · Cited by 89 · see citing works
Fontanella, R., Pelagalli, A., Nardelli, A., D'Alterio, C., Ieranò, C., Cerchia, L., Lucarelli, E., Scala, S., & Zannetti, A. (2016) · Cancer Letters · doi:10.1016/j.canlet.2015.10.018 · Cited by 79 · see citing works
Support of Tumor Endothelial Cells by Chemokine Receptors
Salazar, N., & Zabel, B. A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00147 · Cited by 72 · see citing works
Deciphering mechanisms of brain metastasis in melanoma - the gist of the matter
Redmer, T. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0854-5 · Cited by 67 · see citing works
Chemokine-protease interactions in cancer
Van Damme, J., Struyf, S., & Opdenakker, G. (2004) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2003.10.007 · Cited by 71 · see citing works
Altenburg, J. D., & Siddiqui, R. A. (2009) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-08-0385 · Cited by 67 · see citing works
Powell, D. R., Blasky, A. J., Britt, S. G., & Artinger, K. B. (2013) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1224 · Cited by 62 · see citing works
A microfluidic model for organ-specific extravasation of circulating tumor cells
Riahi, R., Yang, Y. L., Kim, H., Jiang, L., Wong, P. K., & Zohar, Y. (2014) · Biomicrofluidics · doi:10.1063/1.4868301 · Cited by 60 · see citing works
Senescent fibroblast-derived Chemerin promotes squamous cell carcinoma migration
Farsam, V., Basu, A., Gatzka, M., Treiber, N., Schneider, L. A., Mulaw, M. A., Lucas, T., Kochanek, S., Dummer, R., Levesque, M. P., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.13446 · Cited by 59 · see citing works
Bone Marrow Stem Cell Chemotactic Activity Is Induced by Elevated CXCl12 in Endometriosis
Moridi, I., Mamillapalli, R., Cosar, E., Ersoy, G. S., & Taylor, H. S. (2017) · Reproductive Sciences · doi:10.1177/1933719116672587 · Cited by 59 · see citing works
Modular Hydrogel Vaccine for Programmable and Coordinate Elicitation of Cancer Immunotherapy
Ji, P., Sun, W., Zhang, S., Xing, Y., Wang, C., Wei, M., Li, Q., Ji, G., & Yang, G. (2023) · Advanced Science · doi:10.1002/advs.202301789 · Cited by 57 · see citing works
Lin, B.-R., Chang, C.-C., Chen, L.-R., Wu, M.-H., Wang, M.-Y., Kuo, I.-H., Chu, C.-Y., Chang, K.-J., Lee, P.-H., Chen, W.-J., et al. (2007) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-06-0289 · Cited by 51 · see citing works
Clinical and therapeutic implications of follistatin in solid tumours
SHI, L., RESAUL, J., OWEN, S., YE, L., & JIANG, W. G. (2016) · Cancer Genomics & Proteomics · doi:10.21873/cgp.20005 · Cited by 47 · see citing works
Moran, D. M., & Maki, C. G. (2010) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-09-1220 · Cited by 35 · see citing works
Tumor interactions with soluble factors and the nervous system
Voss, M. J., & Entschladen, F. (2010) · Cell Communication and Signaling · doi:10.1186/1478-811x-8-21 · Cited by 25 · see citing works
Modulating chemotaxis of lung cancer cells by using electric fields in a microfluidic device
Kao, Y.-C., Hsieh, M.-H., Liu, C.-C., Pan, H.-J., Liao, W.-Y., Cheng, J.-Y., Kuo, P.-L., & Lee, C.-H. (2014) · Biomicrofluidics · doi:10.1063/1.4870401 · Cited by 19 · see citing works
- Authors
- Müller, A., Homey, B., Soto, H., Ge, N., Catron, D., Buchanan, M. E., McClanahan, T., Murphy, E., Yuan, W., Wagner, S. N., Barrera, J. L., Mohar, A., Verástegui, E., & Zlotnik, A.
- Affiliations
- Heinrich Heine University Düsseldorf (DE)
- University of Duisburg-Essen (DE)
- Instituto Nacional de Cancerología (MX)
- Corresponding author
- Zlotnik, Albert
- ORCID
- Venue
- Nature
- Published
- 2001-03
- Volume
- 410
- Issue
- 6824
- Pages
- 50-56
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2156323704
- Cited by
- 5,340
- References
- 40
- Citations by year
- 2026: 63 · 2025: 109 · 2024: 133 · 2023: 175 · 2022: 133 · 2021: 183 · 2020: 173 · 2019: 167 · 2018: 202 · 2017: 190 · 2016: 203 · 2015: 276 · 2014: 273 · 2013: 258 · 2012: 272
- FWCI
- 87.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- breast cancer metastasis, chemokine receptors, CXCR4, CCR7, CCR10, actin polymerization, pseudopodia formation, tumor invasion, lymph node metastasis, lung metastasis, leukocyte migration
- MeSH terms
- Actins, Animals, Blood Proteins, Breast Neoplasms, Chemotaxis, Humans, Lung, Lymphatic Metastasis, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasm Transplantation, Tumor Cells, Cultured, Mice, SCID, Receptors, Chemokine, Receptors, CXCR4, Chemokines, CXC, Mice, Chemokine CXCL12, Receptors, CCR7
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
