The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Cancer-associated fibroblast exosomes regulate survival and proliferation of pancreatic cancer cells
Open accessAbstract
Cancer-associated fibroblasts (CAFs) comprise the majority of the tumor bulk of pancreatic ductal adenocarcinomas (PDACs). Current efforts to eradicate these tumors focus predominantly on targeting the proliferation of rapidly growing cancer epithelial cells. We know that this is largely ineffective with resistance arising in most tumors following exposure to chemotherapy. Despite the long-standing recognition of the prominence of CAFs in PDAC, the effect of chemotherapy on CAFs and how they may contribute to drug resistance in neighboring cancer cells is not well characterized. Here, we show that CAFs exposed to chemotherapy have an active role in regulating the survival and proliferation of cancer cells. We found that CAFs are intrinsically resistant to gemcitabine, the chemotherapeutic standard of care for PDAC. Further, CAFs exposed to gemcitabine significantly increase the release of extracellular vesicles called exosomes. These exosomes increased chemoresistance-inducing factor, Snail, in recipient epithelial cells and promote proliferation and drug resistance. Finally, treatment of gemcitabine-exposed CAFs with an inhibitor of exosome release, GW4869, significantly reduces survival in co-cultured epithelial cells, signifying an important role of CAF exosomes in chemotherapeutic drug resistance. Collectively, these findings show the potential for exosome inhibitors as treatment options alongside chemotherapy for overcoming PDAC chemoresistance.
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Increased Survival in Pancreatic Cancer with nab-Paclitaxel plus Gemcitabine
Von Hoff, D. D., Ervin, T., Arena, F. P., Chiorean, E. G., Infante, J., Moore, M., Seay, T., Tjulandin, S. A., Ma, W. W., Saleh, M. N., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1304369 · Cited by 6,712
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
Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis
Zhou, W., Fong, M. Y., Min, Y., Somlo, G., Liu, L., Palomares, M. R., Yu, Y., Chow, A., O’Connor, S. T. F., Chin, A. R., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.03.007 · Cited by 1,476 · cited 1×
“Several studies have shown that exosomal-derived miRNAs promote metastases (15) and enhance endothelial cell migration (16).”
Exosomes Mediate Stromal Mobilization of Autocrine Wnt-PCP Signaling in Breast Cancer Cell Migration
Luga, V., Zhang, L., Viloria-Petit, A. M., Ogunjimi, A. A., Inanlou, M. R., Chiu, E., Buchanan, M., Hosein, A. N., Basik, M., & Wrana, J. L. (2012) · Cell · doi:10.1016/j.cell.2012.11.024 · Cited by 1,311 · cited 2×
“Recent studies show oncogenic exosomes can promote invasion (12), deliver oncogenic DNA to normal cells (31), increase drug resistance of cancer cells (32, 33), and can prime distant organs for metastasis (34–36).”
An Undesired Effect of Chemotherapy
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Cited by
Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance
Mashouri, L., Yousefi, H., Aref, A. R., Ahadi, A. M., Molaei, F., & Alahari, S. K. (2019) · Molecular Cancer · doi:10.1186/s12943-019-0991-5 · Cited by 1,363
Clinical and therapeutic relevance of cancer-associated fibroblasts
Chen, Y., McAndrews, K. M., & Kalluri, R. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00546-5 · Cited by 1,230
Exosomes: key players in cancer and potential therapeutic strategy
Dai, J., Su, Y., Zhong, S., Cong, L., Liu, B., Yang, J., Tao, Y., He, Z., Chen, C., & Jiang, Y. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00261-0 · Cited by 1,186
Hu, J. L., Wang, W., Lan, X. L., Zeng, Z. C., Liang, Y. S., Yan, Y. R., Song, F. Y., Wang, F. F., Zhu, X. H., Liao, W. J., et al. (2019) · Molecular Cancer · doi:10.1186/s12943-019-1019-x · Cited by 773
Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer
Wu, F., Yang, J., Liu, J., Wang, Y., Mu, J., Zeng, Q., Deng, S., & Zhou, H. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00641-0 · Cited by 773
Metadata
- Authors
- Richards, K. E., Zeleniak, A. E., Fishel, M. L., Wu, J., Littlepage, L. E., & Hill, R.
- Venue
- Oncogene
- Published
- 2016-09-26
- Volume
- 36
- Issue
- 13
- Pages
- 1770-1778
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2433751364
- Cited by
- 735
- References
- 6
- FWCI
- 24.68
- Type
- journal article
- Language
- en
- Open access
- green
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