Abstract B107: STAT3-induced production of hyaluronan contributes to FGFR-induced migration, proliferation, and therapeutic resistance in breast cancer
| Autor: | Kaylee Schwertfeger, Polly Chuntova, James B. McCarthy, Laura R. Bohrer |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Cancer Research
animal structures Extracellular matrix component Cancer Biology Hyaluronan Synthase 2 medicine.disease Proinflammatory cytokine Oncology Fibroblast growth factor receptor embryonic structures Cancer research medicine biology.protein Signal transduction Autocrine signalling STAT3 Molecular Biology |
| Zdroj: | Molecular Cancer Research. 11:B107-B107 |
| ISSN: | 1557-3125 1541-7786 |
| Popis: | Aberrant activation of fibroblast growth factor receptors (FGFRs) has been linked to breast cancer growth and progression. FGFR activation in tumor cells acts through both autocrine and paracrine mechanisms to contribute to tumor growth. Our previous studies suggesting that FGFR activation leads to increased inflammation led us to evaluate the mechanisms that drive FGFR-induced inflammation in the tumor setting. We demonstrate here that FGFR activation leads to phosphorylation of STAT3Tyr705 in a number of breast cancer cell lines. Furthermore, we demonstrate that phosphorylation of STAT3Tyr705 is mediated indirectly through FGFR-induced production of IL-6 family cytokines. Using a novel in vivo model of FGFR-dependent tumor growth, we demonstrate that pharmacological inhibition of STAT3 leads to decreased FGFR tumor growth. Further examination of the function of STAT3 in this model revealed that STAT3 regulates expression of hyaluronan synthase 2 (Has2) and subsequent production of the extracellular matrix component hyaluronan (HA). Increased HA production by the tumor cells was found to contribute to FGFR-induced proliferation, migration and therapeutic resistance. Finally, analysis of human breast cancer samples reveals a correlation between activated FGFR signaling and tumor-associated expression of HA. In conclusion, our studies demonstrate that FGFR activation leads to STAT3 activity, which regulates expression of Has2 and production of tumor cell-derived HA. Together, these results identify a novel pathway by which FGFR induces proinflammatory signaling pathways and modifies the microenvironment, leading to enhanced FGFR-induced tumor growth. Citation Format: Laura Bohrer, Polly Chuntova, James McCarthy, Kaylee Schwertfeger. STAT3-induced production of hyaluronan contributes to FGFR-induced migration, proliferation, and therapeutic resistance in breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; Oct 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2013;11(10 Suppl):Abstract nr B107. |
| Databáze: | OpenAIRE |
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