The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
TGF-β Modulates Ovarian Cancer Invasion by Upregulating CAF-Derived Versican in the Tumor Microenvironment
Open accessAbstract
TGF-β has limited effects on ovarian cancer cells, but its contributions to ovarian tumor growth might be mediated through elements of the tumor microenvironment. In the present study, we tested the hypothesis that TGF modulates ovarian cancer progression by modulating the contribution of cancer-associated fibroblasts (CAF) that are present in the microenvironment. Transcriptome profiling of microdissected stromal and epithelial components of high-grade serous ovarian tumors and TGF-β–treated normal ovarian fibroblasts identified versican (VCAN) as a key upregulated target gene in CAFs. Functional evaluations in coculture experiments showed that TGF-β enhanced the aggressiveness of ovarian cancer cells by upregulating VCAN in CAFs. VCAN expression was regulated in CAFs through TGF-β receptor type II and SMAD signaling. Upregulated VCAN promoted the motility and invasion of ovarian cancer cells by activating the NF-κB signaling pathway and by upregulating expression of CD44, matrix metalloproteinase-9, and the hyaluronan-mediated motility receptor. Our work identified a TGF-β–inducible gene signature specific to CAFs in advanced high-grade serous ovarian tumors, and showed how TGF-β stimulates ovarian cancer cell motility and invasion by upregulating the CAF-specific gene VCAN. These findings suggest insights to develop or refine strategies for TGF-β–targeted therapy of ovarian cancer. Cancer Res; 73(16); 5016–28. ©2013 AACR.
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Siegel, R., Naishadham, D., & Jemal, A. (2012) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.20138 · Cited by 10,679
TGF-ß Signaling in Fibroblasts Modulates the Oncogenic Potential of Adjacent Epithelia
Bhowmick, N. A., Chytil, A., Plieth, D., Gorska, A. E., Dumont, N., Shappell, S., Washington, M. K., Neilson, E. G., & Moses, H. L. (2004) · Science · doi:10.1126/science.1090922 · Cited by 1,401
Know thy neighbor: stromal cells can contribute oncogenic signals
Tlsty, T. D., & Hein, P. W. (2001) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(00)00156-8 · Cited by 425
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Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer
Bowtell, D. D., Böhm, S., Ahmed, A. A., Aspuria, P.-J., Bast, R. C., Beral, V., Berek, J. S., Birrer, M. J., Blagden, S., Bookman, M. A., et al. (2015) · Nature Reviews Cancer · doi:10.1038/nrc4019 · Cited by 1,367
Self-citationThe biology and role of CD44 in cancer progression: Therapeutic implications
Chen, C., Zhao, S., Karnad, A., & Freeman, J. W. (2018) · Journal of Hematology & Oncology · doi:10.1186/s13045-018-0605-5 · Cited by 1,245
Yuan, Z., Li, Y., Zhang, S., Wang, X., Dou, H., Yu, X., Zhang, Z., Yang, S., & Xiao, M. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01744-8 · Cited by 977
Ren, J., Ding, L., Zhang, D., Shi, G., Xu, Q., Shen, S., Wang, Y., Wang, T., & Hou, Y. (2018) · Theranostics · doi:10.7150/thno.25541 · Cited by 698
Chakravarthy, A., Khan, L., Bensler, N. P., Bose, P., & De Carvalho, D. D. (2018) · Nature Communications · doi:10.1038/s41467-018-06654-8 · Cited by 656
Metadata
- Authors
- Yeung, T.-L., Leung, C. S., Wong, K.-K., Samimi, G., Thompson, M. S., Liu, J., Zaid, T. M., Ghosh, S., Birrer, M. J., & Mok, S. C.
- Venue
- Cancer Research
- Published
- 2013-08-13
- Volume
- 73
- Issue
- 16
- Pages
- 5016-5028
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2166607774
- Cited by
- 394
- References
- 3
- FWCI
- 8.88
- Type
- journal article
- Language
- en
- Open access
- green
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- Yeung, T.-L., Leung, C. S., Wong, K.-K., Samimi, G., Thompson, M. S., Liu, J., Zaid, T. M., Ghosh, S., Birrer, M. J., & Mok, S. C. (2013). TGF-β Modulates Ovarian Cancer Invasion by Upregulating CAF-Derived Versican in the Tumor Microenvironment. Cancer Research. https://doi.org/10.1158/0008-5472.can-13-0023
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