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Tissue-resident stem cells promote breast cancer growth and metastasis
Open accessAbstract
Mesenchymal stem cells derived from bone marrow have recently been described to localize to breast carcinomas and to integrate into the tumor-associated stroma. In the present study, we investigated whether adipose tissue-derived stem cells (ASCs) could play a role in tumor growth and invasion. Compared with bone marrow-derived cells, ASCs as tissue-resident stem cells are locally adjacent to breast cancer cells and may interact with tumor cells directly. Here, we demonstrate that ASCs cause the cancer to grow significantly faster when added to a murine breast cancer 4T1 cell line. We further show that breast cancer cells enhance the secretion of stromal cell-derived factor-1 from ASCs, which then acts in a paracrine fashion on the cancer cells to enhance their motility, invasion and metastasis. The tumor-promoting effect of ASCs was abolished by knockdown of the chemokine C-X-C receptor 4 in 4T1 tumor cells. We demonstrated that ASCs home to tumor site and promote tumor growth not only when co-injected locally but also when injected intravenously. Furthermore, we demonstrated that ASCs incorporate into tumor vessels and differentiate into endothelial cells. The tumor-promoting effect of tissue-resident stem cells was also tested and validated using a human breast cancer line MDA-MB-231 cells and human adipose tissue-derived stem cells. Our findings indicate that the interaction of local tissue-resident stem cells with tumor stem cells plays an important role in tumor growth and metastasis.
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“Another MSC-secreted pro-metastasis cytokine, CCL5 (RANTES), can be secreted upon interaction with cancer cells and is associated with tumor progression and invasion in various cancers [73, 87, 100, 142–144].”
From Mesenchymal stem cell secretome and regenerative therapy after cancer (2013) · cites this paper as [73]
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Cites
Multilineage Cells from Human Adipose Tissue: Implications for Cell-Based Therapies
Zuk, P. A., Zhu, M., Mizuno, H., Huang, J., Futrell, J. W., Katz, A. J., Benhaim, P., Lorenz, H. P., & Hedrick, M. H. (2001) · Tissue Engineering · doi:10.1089/107632701300062859 · Cited by 7,956
Human Adipose Tissue Is a Source of Multipotent Stem Cells
Zuk, P. A., Zhu, M., Ashjian, P. H., Ugarte, D. A. D., Huang, J. I., Mizuno, H., Alfonso, Z. C., Fraser, J. K., Benhaim, P., & Hedrick, M. H. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.e02-02-0105 · Cited by 6,762
Orimo, 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
Mesenchymal stem cells within tumour stroma promote breast cancer metastasis
Karnoub, A. E., Dash, A. B., Vo, A. P., Sullivan, A., Brooks, M. W., Bell, G. W., Richardson, A. L., Polyak, K., Tubo, R., & Weinberg, R. A. (2007) · Nature · doi:10.1038/nature06188 · Cited by 3,206
In vitro propagation and transcriptional profiling of human mammary stem/progenitor cellsPreprint
Dontu, G., Abdallah, W. M., Foley, J. M., Jackson, K. W., Clarke, M. F., Kawamura, M., & Wicha, M. S. (2003) · Genes & Development · doi:10.1101/gad.1061803 · Cited by 2,413
Stromal fibroblasts in cancer initiation and progression
Bhowmick, N. A., Neilson, E. G., & Moses, H. L. (2004) · Nature · doi:10.1038/nature03096 · Cited by 2,354
Cancer and the chemokine network
Balkwill, F. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1388 · Cited by 2,343
Ponti, D., Costa, A., Zaffaroni, N., Pratesi, G., Petrangolini, G., Coradini, D., Pilotti, S., Pierotti, M. A., & Daidone, M. G. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-0626 · Cited by 1,725
Carcinoma-associated fibroblasts stimulate tumor progression of initiated human epithelium
Olumi, A., Grossfeld, G., Hayward, S., Carroll, P., Cunha, G., Hein, P., & Tlsty, T. (2000) · Breast Cancer Research · doi:10.1186/bcr138 · Cited by 1,463
Role of tissue stroma in cancer cell invasion
De Wever, O., & Mareel, M. (2003) · The Journal of Pathology · doi:10.1002/path.1398 · Cited by 1,042
Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells
Mishra, P. J., Mishra, P. J., Humeniuk, R., Medina, D. J., Alexe, G., Mesirov, J. P., Ganesan, S., Glod, J. W., & Banerjee, D. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-0943 · Cited by 912
Improvement of Postnatal Neovascularization by Human Adipose Tissue-Derived Stem Cells
Miranville, A., Heeschen, C., Sengenès, C., Curat, C. A., Busse, R., & Bouloumié, A. (2004) · Circulation · doi:10.1161/01.cir.0000135466.16823.d0 · Cited by 899
Neurogenic differentiation of murine and human adipose-derived stromal cells
Safford, K. M., Hicok, K. C., Safford, S. D., Halvorsen, Y. C., Wilkison, W. O., Gimble, J. M., & Rice, H. E. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)00469-2 · Cited by 756
CXCR4 Regulates Growth of Both Primary and Metastatic Breast Cancer
Smith, M. C. P., Luker, K. E., Garbow, J. R., Prior, J. L., Jackson, E. N., Piwnica-Worms, D. R., & Luker, G. D. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-1844 · Cited by 715
Chondrogenic Potential of Adipose Tissue-Derived Stromal Cells in Vitro and in Vivo
Erickson, G. R., Gimble, J. M., Franklin, D. M., Rice, H. E., Awad, H. A., & Guilak, F. (2002) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.6270 · Cited by 675
Fundamental Concepts of the Angiogenic Process
Folkman, J. (2003) · Current Molecular Medicine · doi:10.2174/1566524033479465 · Cited by 666
Kilroy, G. E., Foster, S. J., Wu, X., Ruiz, J., Sherwood, S., Heifetz, A., Ludlow, J. W., Stricker, D. M., Potiny, S., Green, P., et al. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21068 · Cited by 642
A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors
Rubin, J. B., Kung, A. L., Klein, R. S., Chan, J. A.-W., Sun, Y., Schmidt, K. F., Kieran, M. W., Luster, A. D., & Segal, R. A. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2235846100 · Cited by 615
Tai, M. (2004) · Carcinogenesis · doi:10.1093/carcin/bgh321 · Cited by 591
Stem cells in normal breast development and breast cancer
Dontu, G., Al‐Hajj, M., Abdallah, W. M., Clarke, M. F., & Wicha, M. S. (2003) · Cell Proliferation · doi:10.1046/j.1365-2184.36.s.1.6.x · Cited by 591
Zannettino, A. C. W., Paton, S., Arthur, A., Khor, F., Itescu, S., Gimble, J. M., & Gronthos, S. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21210 · Cited by 553
Stem cells in normal breast development and breast cancer
Wicha, M., Dontu, G., Al‐Hajj, M., & Clarke, M. F. (2003) · Breast Cancer Research · doi:10.1186/bcr709 · Cited by 536
Differentiation of human adipose stromal cells into hepatic lineage in vitro and in vivo
Seo, M. J., Suh, S. Y., Bae, Y. C., & Jung, J. S. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.12.158 · Cited by 530
Timper, K., Seboek, D., Eberhardt, M., Linscheid, P., Christ‐Crain, M., Keller, U. B., Müller-Stich, B. P., & Zulewski, H. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.01.072 · Cited by 459
Rønnov‐Jessen, L., PETERSEN, O. W., Koteliansky, V., & Bissell, M. J. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117736 · Cited by 443
Role of high expression levels of CXCR4 in tumor growth, vascularization, and metastasis
Darash‐Yahana, M., Pikarsky, E., Abramovitch, R., Zeira, E., Pal, B., Karplus, R., Beider, K., Avniel, S., Kasem, S., Galun, E., et al. (2004) · The FASEB Journal · doi:10.1096/fj.03-0935fje · Cited by 427
Multipotent Stromal Cells Derived From the Infrapatellar Fat Pad of the Knee
Wickham, M. Q., Erickson, G. R., Gimble, J. M., Vail, T. P., & Guilak, F. (2003) · Clinical Orthopaedics and Related Research · doi:10.1097/01.blo.0000072467.53786.ca · Cited by 426
Iyengar, P., Combs, T. P., Shah, S. J., Gouon–Evans, V., Pollard, J. W., Albanese, C., Flanagan, L., Tenniswood, M., Guha, C., Lisanti, M. P., et al. (2003) · Oncogene · doi:10.1038/sj.onc.1206737 · Cited by 372
Concentration-dependent inhibition of angiogenesis by mesenchymal stem cells
Otsu, K., Das, S., Houser, S., Quadri, S. K., Bhattacharya, S., & Bhattacharya, J. (2008) · Blood · doi:10.1182/blood-2008-09-176198 · Cited by 348
Smooth‐muscle differentiation in stromal cells of malignant and non‐malignant breast tissues
Sappino, A. P., Skalli, O., Jackson, B. W., Schürch, W., & Gabbiani, G. (1988) · International Journal of Cancer · doi:10.1002/ijc.2910410512 · Cited by 325
The cardioprotective effect of mesenchymal stem cells is mediated by IGF-I and VEGF
Sadat, S., Gehmert, S., Song, Y., Yen, Y., Bai, X., Gaiser, S., Klein, H., & Alt, E. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.09.058 · Cited by 302
Self-citationBone-marrow-derived myofibroblasts contribute to the cancer-induced stromal reaction
Ishii, G., Sangai, T., Oda, T., Aoyagi, Y., Hasebe, T., Kanomata, N., Endoh, Y., Okumura, C., Okuhara, Y., Magae, J., et al. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)01544-4 · Cited by 281
Krampera, M., Marconi, S., Pasini, A., Galiè, M., Rigotti, G., Mosna, F., Tinelli, M., Lovato, L., Anghileri, E., Andreini, A., et al. (2006) · Bone · doi:10.1016/j.bone.2006.09.006 · Cited by 241
Altman, A. M., Yan, Y., Matthias, N., Bai, X., Ríos, C. N., Mathur, A. B., Song, Y.-H., & Alt, E. (2008) · Stem Cells · doi:10.1634/stemcells.2008-0178 · Cited by 232
Self-citationManabe, Y., Toda, S., Miyazaki, K., & Sugihara, H. (2003) · The Journal of Pathology · doi:10.1002/path.1430 · Cited by 231
Adipose-derived stromal cells—their utility and potential in bone formation
Halvorsen, Y. D., Wilkison, W. O., & Gimble, J. (2000) · International Journal of Obesity · doi:10.1038/sj.ijo.0801503 · Cited by 224
CXC chemokines in angiogenesis of cancer
Strieter, R. M., Belperio, J. A., Phillips, R. J., & Keane, M. P. (2004) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2003.10.006 · Cited by 222
Cornil, I., Theodorescu, D., Man, S., Herlyn, M., Jambrosic, J., & Kerbel, R. S. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.14.6028 · Cited by 217
Halvorsen, Y. C., Bond, A., Sen, A., Franklin, D. M., Lea-Currie, Y. R., Sujkowski, D., Ellis, P. N., Wilkison, W. O., & Gimble, J. M. (2001) · Metabolism · doi:10.1053/meta.2001.21690 · Cited by 200
Goldmann, E. (1908) · PubMed · Cited by 179
Brand, S., Dambacher, J., Beigel, F., Olszak, T., Diebold, J., Otte, J., Göke, B., & Eichhorst, S. T. (2005) · Experimental Cell Research · doi:10.1016/j.yexcr.2005.07.006 · Cited by 175
Dermal matrix as a carrier for in vivo delivery of human adipose-derived stem cells
Altman, A. M., Matthias, N., Yan, Y., Song, Y., Bai, X., Chiu, E. S., Slakey, D. P., & Alt, E. (2008) · Biomaterials · doi:10.1016/j.biomaterials.2007.11.026 · Cited by 172
Self-citationNeurogenesis of Rhesus adipose stromal cells
Kang, S. K., Putnam, L. A., Ylöstalo, J., Popescu, I., Dufour, J., Belousov, A. B., & Bunnell, B. A. (2004) · Journal of Cell Science · doi:10.1242/jcs.01264 · Cited by 163
Lee, J.-H., & Kemp, D. M. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.01.038 · Cited by 158
Rat Extramedullary Adipose Tissue as a Source of Osteochondrogenic Progenitor Cells
Huang, J. I., Beanes, S. R., Zhu, M., Lorenz, H. P., Hedrick, M. H., & Benhaim, P. (2002) · Plastic & Reconstructive Surgery · doi:10.1097/00006534-200203000-00037 · Cited by 150
Chauhan, H. A., Abraham, A., Phillips, J. R. A., Pringle, J. H., Walker, R. A., & Jones, J. L. (2003) · Journal of Clinical Pathology · doi:10.1136/jcp.56.4.271 · Cited by 148
Kao, C., Nomata, K., Oakley, C. S., Welsch, C. W., & Chang, C. (1995) · Carcinogenesis · doi:10.1093/carcin/16.3.531 · Cited by 142
Corre, J., Barreau, C., Cousin, B., Chavoin, J.-P., Caton, D., Fournial, G., Pénicaud, L., Casteilla, L., & Laharrague, P. F. (2006) · Journal of Cellular Physiology · doi:10.1002/jcp.20655 · Cited by 132
Ohira, S., Sasaki, M., Harada, K., Sato, Y., Zen, Y., Isse, K., Kozaka, K., Ishikawa, A., Oda, K., Nimura, Y., et al. (2006) · American Journal Of Pathology · doi:10.2353/ajpath.2006.050204 · Cited by 120
Chang, C., Sun, W. T., Cruz, A., Saitoh, M., Tai, M.-H., & Trosko, J. E. (2001) · Radiation Research · doi:10.1667/0033-7587(2001)155[0201:ahbect]2.0.co;2 · Cited by 106
Electrophysiological properties of human adipose tissue-derived stem cells
Bai, X., Ma, J., Pan, Z. Z., Song, Y., Freyberg, S., Yan, Y., Vykoukal, D. M., & Alt, E. (2007) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00089.2007 · Cited by 98
Self-citationStromal Cell-Derived Factor-1 Promotes Cell Migration, Tumor Growth of Colorectal Metastasis
Kollmar, O., Rupertus, K., Scheuer, C., Junker, B., Tilton, B., Schilling, M. K., & Menger, M. D. (2007) · Neoplasia · doi:10.1593/neo.07559 · Cited by 96
Human mesenchymal stem cells from adipose tissue: Differentiation into hepatic lineage
Taléns‐Visconti, R., Ana Bonora-Centelles, A., Jover, R., Mirabet, V., Carbonell, F., Castell, J. V., & Gómez‐Lechón, M. J. (2006) · Toxicology in Vitro · doi:10.1016/j.tiv.2006.08.009 · Cited by 93
THE GROWTH OF MALIGNANT DISEASE IN MAN AND THE LOWER ANIMALS,
Goldmann, E. (1907) · The Lancet · doi:10.1016/s0140-6736(01)65002-5 · Cited by 84
Sun, W., Kang, K., Morita, I., Trosko, J. E., & Chang, C. (1999) · PubMed · Cited by 71
Kang, K. (1997) · Carcinogenesis · doi:10.1093/carcin/18.2.251 · Cited by 68
Recent translational research: stem cells as the roots of breast cancer
Chang, C. (2006) · Breast Cancer Research · doi:10.1186/bcr1385 · Cited by 61
Milne, M. L., Quail, J. M., Rosen, C. J., & Baran, D. T. (2001) · Journal of Cellular Biochemistry · doi:10.1002/1097-4644(20010501)81:2 · Cited by 43
Kang, K., Sun, W. T., Nomata, K., Morita, I., Cruz, A., Liu, C., Trosko, J. E., & Chang, C. (1998) · Molecular Carcinogenesis · doi:10.1002/(sici)1098-2744(199804)21:4 · Cited by 43
Ahn, E. H., Chang, C., & Schroeder, J. J. (2006) · Experimental Biology and Medicine · doi:10.1177/153537020623101012 · Cited by 42
Kao, C., Oakley, C. S., Welsch, C. W., & Chang, C. (1997) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1007/s11626-997-0048-8 · Cited by 36
Flora, S. D., Scarfı̀, S., Izzotti, A., D’Agostini, F., Chang, C., Bagnasco, M., FLORA, A. D., & Trosko, J. E. (2006) · International Journal of Oncology · doi:10.3892/ijo.29.3.521 · Cited by 30
VEGF receptor Flk‐1 plays an important role in c‐kit expression in adipose tissue derived stem cells
Bai, X., Sadat, S., Gehmert, S., Alt, E., & Song, Y. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.08.063 · Cited by 30
Self-citationPark, J.-S., Noh, D., Kim, S.-H., Kim, S., Kong, G., Chang, C., Lee, Y.-S., Trosko, J. E., & Kang, K. (2004) · PubMed · Cited by 19
Schimrosczyk, K., Song, Y., Vykoukal, J. V., Vykoukal, D. M., Bai, X., Krohn, A., Freyberg, S., & Alt, E. (2008) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.1080/00365510701836907 · Cited by 12
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Flagged first, then by citations
6 of the 71 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Hsieh, 1999, Stem cell differentiation and reduction as a potential mechanism for chemoprevention of breast cancer, Chinese Pharm. J., 51, 15
- Chang, 2000, Roles of ionizing radiation in neoplastic transformation of human breast epithelial cells, 576
Cited by
Sorted by citations
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Vizoso, F., Eiro, N., Cid, S., Schneider, J., & Perez-Fernandez, R. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18091852 · Cited by 1,363
Stromal cells in tumor microenvironment and breast cancer
Mao, Y., Keller, E. T., Garfield, D. H., Shen, K., & Wang, J. (2013) · Cancer and Metastasis Reviews · doi:10.1007/s10555-012-9415-3 · Cited by 671
Klopp, A. H., Gupta, A., Spaeth, E., Andreeff, M., & Marini, F. (2011) · Stem Cells · doi:10.1002/stem.559 · Cited by 562
The Potential of Adipose Stem Cells in Regenerative Medicine
Lindroos, B., Suuronen, R., & Miettinen, S. (2010) · Stem Cell Reviews and Reports · doi:10.1007/s12015-010-9193-7 · Cited by 443
McLean, K., Gong, Y., Choi, Y., Deng, N., Yang, K., Bai, S., Cabrera, L., Keller, E., McCauley, L., Cho, K. R., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci45273 · Cited by 380
Metadata
- Authors
- Muehlberg, F. L., Song, Y.-H., Krohn, A., Pinilla, S. P., Droll, L. H., Leng, X., Seidensticker, M., Ricke, J., Altman, A. M., Devarajan, E., Liu, W., Arlinghaus, R. B., & Alt, E. U.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- University Hospital Magdeburg (DE)
- Corresponding author
- Alt, Eckhard U.
- ORCID
- Venue
- Carcinogenesis
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-01-30
- Volume
- 30
- Issue
- 4
- Pages
- 589-597
- ISSN
- 0143-3334 (ISSN-L)
- 1460-2180
- OpenAlex
- W2107402669
- Cited by
- 330
- References
- 71
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 13 · 2023: 9 · 2022: 11 · 2021: 19 · 2020: 10 · 2019: 17 · 2018: 18 · 2017: 13 · 2016: 20 · 2015: 33 · 2014: 35 · 2013: 24 · 2012: 31
- FWCI
- 16.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Carcinogenesis (publishedVersion)
- PubMed (publishedVersion)
- BORIS (University Library Bern) (submittedVersion, other-oa)
- Open Access CRIS of the University of Bern
- Funders
- U.S. Department of Defense (W81XWH, W81XWH0810523)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- tissue-resident stem cells, adipose-derived stem cells, breast cancer, tumor growth, metastasis, CXCL12, CXCR4, paracrine signaling, tumor cell motility, tumor invasion, stem cell homing, tumor vasculature, endothelial differentiation, tumor microenvironment, 4T1 cells, MDA-MB-231 cells
- MeSH terms
- Adipose Tissue, Animals, Cell Movement, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Lung Neoplasms, Male, Mice, Inbred BALB C, Mice, Nude, Neoplasm Invasiveness, Neovascularization, Pathologic, Neoplastic Stem Cells, Blotting, Western, Mammary Neoplasms, Animal, Stromal Cells, Spheroids, Cellular, Receptors, CXCR4, Vascular Endothelial Growth Factor A, Immunoprecipitation, Mice, Chemokine CXCL12
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