Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo
Abstract
Mesenchymal stem cells (MSCs) can promote tumor growth in a mouse xenograft model, but the exact mechanism remains unclear. In this study, we investigated the effects of bone marrow MSC-derived exosomes (MSC-exosomes) on tumor growth in vitro and in vivo. Our results showed that MSC-exosomes promoted tumor growth in vivo. MSC-exosomes enhanced vascular endothelial growth factor (VEGF) expression in tumor cells by activating extracellular signal-regulated kinase1/2 (ERK1/2) pathway. Inhibition of ERK1/2 activation reserved the increase of VEGF level by MSC-exosomes. Our findings demonstrate a new mechanism through which MSC-exosome-mediated cell-cell interactions may contribute to tumor progression.
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The utilization of exosomes in cancer cell cultures was based on an exosome concentration of 100-400 μg/ml reported in the literature.
“The utilization of exosomes in cancer cell cultures were based on application of 100–400 μg/ml of exosomes concentration that has been reported in literature (Christianson et al., 2013; Zhu et al., 2012).”
From Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism (2016) · cites this paper as Zhu et al., 2012
Cites
Multilineage potential of adult human mesenchymal stem cells
Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., Moorman, M. A., Simonetti, D. W., Craig, S., & Marshak, D. R. (1999) · Science · doi:10.1126/science.284.5411.143 · Cited by 21,052 · see citing works
Transmission Electron Microscopy
Williams, D. B., & Carter, C. B. (2009) · Springer eBooks · doi:10.1007/978-0-387-76501-3 · Cited by 4,004 · see citing works
B lymphocytes secrete antigen-presenting vesicles.
Raposo, G., Nijman, H. W., Stoorvogel, W., Liejendekker, R., Harding, C. V., Melief, C. J., & Geuze, H. J. (1996) · The Journal of experimental medicine · doi:10.1084/jem.183.3.1161 · Cited by 3,546 · see citing works
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 · see citing works
Exosomes – vesicular carriers for intercellular communication
Simons, M., & Raposo, G. (2009) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2009.03.007 · Cited by 2,351 · see citing works
Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury
Lai, R. C., Arslan, F., Lee, M. M., Sze, N. S. K., Choo, A., Chen, T. S., Salto-Tellez, M., Timmers, L., Lee, C. N., El Oakley, R. M., et al. (2010) · Stem Cell Research · doi:10.1016/j.scr.2009.12.003 · Cited by 2,215 · see citing works
Determination of subcutaneous tumor size in athymic (nude) mice
Tomayko, M. M., & Reynolds, C. P. (1989) · Cancer Chemotherapy and Pharmacology · doi:10.1007/bf00300234 · Cited by 1,830 · see citing works
Mesenchymal Stem Cell-Derived Microvesicles Protect Against Acute Tubular Injury
Bruno, S., Grange, C., Deregibus, M. C., Calogero, R., Saviozzi, S., Collino, F., Morando, L., Busca, A., Falda, M., Bussolati, B., et al. (2009) · Journal of the American Society of Nephrology · doi:10.1681/asn.2008070798 · Cited by 1,332 · see citing works
Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals
Djouad, F., Plence, P., Bony, C., Tropel, P., Apparailly, F., Sany, J., Noël, D., & Jorgensen, C. (2003) · Blood · doi:10.1182/blood-2003-04-1193 · Cited by 1,166 · see citing works
(2002) · PubMed · Cited by 903 · see citing works
Studeny, M., Marini, F. C., Dembinski, J. L., Zompetta, C., Cabreira-Hansen, M. D. G., Bekele, B. N., Champlin, R. E., & Andreeff, M. (2004) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djh299 · Cited by 841 · see citing works
Spaeth, E. L., Dembinski, J. L., Sasser, A. K., Watson, K., Klopp, A., Hall, B., Andreeff, M., & Marini, F. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004992 · Cited by 807 · see citing works
Weber, J. D., Raben, D. M., Phillips, P. J., & Baldassare, J. J. (1997) · Biochemical Journal · doi:10.1042/bj3260061 · Cited by 407 · see citing works
VEGF expression by mesenchymal stem cells contributes to angiogenesis in pancreatic carcinoma
Beckermann, B. M., Kallifatidis, G., Groth, A., Frommhold, D., Apel, A., Mattern, J., Salnikov, A. V., Moldenhauer, G., Wagner, W., Diehlmann, A., et al. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604508 · Cited by 406 · see citing works
Microvesicles: Messengers and mediators of tumor progression
Al-Nedawi, K. N. I., Meehan, B., & Rak, J. W. (2009) · Cell Cycle · doi:10.4161/cc.8.13.8988 · Cited by 401 · see citing works
Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo
Zhu, W., Xu, W., Jiang, R., Qian, H., Chen, M., Hu, J., Cao, W., Han, C., & Chen, Y. (2006) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2005.07.004 · Cited by 386 · see citing works
Self-citationXu, W., Zhang, X., Qian, H., Zhu, W., Sun, X., Hu, J., Zhou, H., & Chen, Y. (2004) · Experimental Biology and Medicine · doi:10.1177/153537020422900706 · Cited by 371 · see citing works
Self-citationCXCR4/CXCL12 axis promotes VEGF-mediated tumor angiogenesis through Akt signaling pathway
Liang, Z., Brooks, J., Willard, M. T., Liang, K., Yoon, Y., Kang, S., & Shim, H. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.05.182 · Cited by 335 · see citing works
Mesenchymal stem cells enhance growth and metastasis of colon cancer
Shinagawa, K., Kitadai, Y., Tanaka, M., Sumida, T., Kodama, M., Higashi, Y., Tanaka, S., Yasui, W., & Chayama, K. (2010) · International Journal of Cancer · doi:10.1002/ijc.25440 · Cited by 308 · see citing works
Gastric cancer exosomes promote tumour cell proliferation through PI3K/Akt and MAPK/ERK activation
Qu, J.-L., Qu, X.-J., Zhao, M.-F., Teng, Y.-E., Zhang, Y., Hou, K., Jiang, Y.-H., Yang, X., & Liu, Y.-P. (2009) · Digestive and Liver Disease · doi:10.1016/j.dld.2009.04.006 · Cited by 303 · see citing works
Paracrine induction of endothelium by tumor exosomes
Hood, J. L., Pan, H., Lanza, G. M., & Wickline, S. A. (2009) · Laboratory Investigation · doi:10.1038/labinvest.2009.94 · Cited by 273 · see citing works
Balmanno, K., & Cook, S. J. (1999) · Oncogene · doi:10.1038/sj.onc.1202647 · Cited by 227 · see citing works
Highlights of a new type of intercellular communication: microvesicle-based information transfer
Pap, E., Pállinger, É., Pásztói, M., & Falus, A. (2009) · Inflammation Research · doi:10.1007/s00011-008-8210-7 · Cited by 205 · see citing works
Camussi, G., Deregibus, M. C., & Tetta, C. (2009) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0b013e328332fb6f · Cited by 168 · see citing works
Roorda, B. D., ter Elst, A., Kamps, W. A., & de Bont, E. S. J. M. (2008) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2008.06.004 · Cited by 129 · see citing works
Recombination of CXCR4, VEGF, and MMP-9 predicting lymph node metastasis in human breast cancer
Li, H., Zhang, C., Qiu, Y., et al. (2007) · Cancer Letters · doi:10.1016/j.canlet.2007.01.005 · Cited by 110 · see citing works
Mesenchymal stem cell-like cells derived from human gastric cancer tissues
Cao, H., Xu, W., Qian, H., Zhu, W., Yan, Y., Zhou, H., Zhang, X., Xu, X., Li, J., Chen, Z., et al. (2008) · Cancer Letters · doi:10.1016/j.canlet.2008.08.036 · Cited by 103 · see citing works
Self-citationAngelot, F., Seillès, E., Biichlé, S., Berda, Y., Gaugler, B., Plumas, J., Chaperot, L., Dignat‐George, F., Tiberghien, P., Saas, P., et al. (2009) · Haematologica · doi:10.3324/haematol.2009.010934 · Cited by 98 · see citing works
Human mesenchymal stem cell transformation is associated with a mesenchymal–epithelial transition
Rubio, D., García, S., de la Cueva, T., Paz, M. F., Lloyd, A. C., Bernad, A., & Garcı́a-Castro, J. (2007) · Experimental Cell Research · doi:10.1016/j.yexcr.2007.11.017 · Cited by 89 · see citing works
Yoshino, Y., Aoyagi, M., Tamaki, M., Duan, L., Morimoto, T., & Ohno, K. (2006) · International Journal of Oncology · doi:10.3892/ijo.29.4.981 · Cited by 84 · see citing works
Multipotent mesenchymal stromal cells and rheumatoid arthritis: risk or benefit?
Bouffi, C., Djouad, F., Mathieu, M., Noël, D., & Jørgensen, C. (2009) · Lara D. Veeken · doi:10.1093/rheumatology/kep162 · Cited by 70 · see citing works
Roorda, B. D., Elst, A. T., Boer, T. G. J. M.-D., Kamps, W. A., & de Bont, E. S. J. M. (2010) · Cancer Investigation · doi:10.3109/07357900903179625 · Cited by 51 · see citing works
Bi, S., Liu, J., Li, Y., Wang, Q., Liu, H.-K., Yan, Y., Chen, B.-Q., & Sun, W. (2010) · Toxicology · doi:10.1016/j.tox.2010.05.002 · Cited by 48 · see citing works
Self-citationAldosterone increases VEGF-A production in human neutrophils through PI3K, ERK1/2 and p38 pathways
Walczak, C., Gaignier, F., Gilet, A., et al. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.07.010 · Cited by 43 · see citing works
Implication of the ERK Pathway on the Post-transcriptional Regulation of VEGF mRNA Stability
Essafi‐Benkhadir, K., Pouysségur, J., & Pagès, G. (2010) · Methods in molecular biology · doi:10.1007/978-1-60761-795-2_28 · Cited by 20 · see citing works
Ma, B., Ren, J., Jiang, H., et al. (2008) · PubMed · Cited by 14 · see citing works
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Zhao, H., Yang, L., Baddour, J., Achreja, A., Bernard, V., Moss, T., Marini, J. C., Tudawe, T., Seviour, E. G., San Lucas, F. A., et al. (2016) · eLife · doi:10.7554/elife.10250 · Cited by 927 · see citing works
Johnsen, K. B., Gudbergsson, J. M., Skov, M. N., Pilgaard, L., Moos, T., & Duroux, M. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.04.005 · Cited by 704 · see citing works
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Ding, Y., Cao, F., Sun, H., Wang, Y., Liu, S., Wu, Y., Cui, Q., Mei, W., & Li, F. (2019) · Cancer Letters · doi:10.1016/j.canlet.2018.10.039 · Cited by 177 · see citing works
Galland, S., & Stamenkovic, I. (2020) · The Journal of Pathology · doi:10.1002/path.5357 · Cited by 165 · see citing works
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Kim, H., Jang, H., Cho, H., Choi, J., Hwang, K. Y., Choi, Y., Kim, S. H., & Yang, Y. (2021) · Cancers · doi:10.3390/cancers13174435 · Cited by 152 · see citing works
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- Authors
- Zhu, W., Huang, L., Li, Y., Zhang, X., Gu, J., Yan, Y., Xu, X., Wang, M., Qian, H., & Xu, W.
- Affiliations
- Jiangsu University (CN)
- Corresponding author
- Xu, Wenrong
- Venue
- Cancer Letters
- Publisher
- Elsevier BV
- Published
- 2012-02
- Volume
- 315
- Issue
- 1
- Pages
- 28-37
- ISSN
- 0304-3835 (ISSN-L)
- OpenAlex
- W2081191481
- Cited by
- 488
- References
- 36
- Citations by year
- 2026: 12 · 2025: 28 · 2024: 31 · 2023: 30 · 2022: 55 · 2021: 50 · 2020: 48 · 2019: 44 · 2018: 37 · 2017: 33 · 2016: 37 · 2015: 25 · 2014: 23 · 2013: 25 · 2012: 10
- FWCI
- 7.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (91129718, 81071421)
- Natural Science Foundation of Jiangsu Province (BK2008232, BE2010703)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- exosomes, mesenchymal stem cells, bone marrow, tumor growth, tumor progression, vascular endothelial growth factor, ERK signaling, intercellular communication, xenograft models
- MeSH terms
- Animals, Bone Marrow Cells, Cell Differentiation, Humans, Immunohistochemistry, Male, Mice, Inbred BALB C, Neoplasms, Xenograft Model Antitumor Assays, Cell Growth Processes, Mice, Exosomes, Mesenchymal Stem Cells
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