Abstract IA24: How tumors regulate their microenvironment in primary sites and metastasis (2013)

Abstract In 1863, Virchow hypothesized that the cancer originated at sites of chronic tissue injury and that the ensuing inflammation they cause enhances cell proliferation. While it is now clear that proliferation of tumor cells alone does not cause cancer, sustained cell proliferation in an environment rich in inflammatory cells, growth factors, activated stroma certainly potentiates and/or promotes neoplastic risk and leads to metastasis. In fact, sometimes the trigger for neoplastic progression may come from signals within the stromal microenvironment. The stromal microenvironment consists of fibroblasts, macrophages, neutrophils, vascular components, nerves and inflammatory cells of the innate and acquired immune response, as well as the extracellular matrix that they elaborate along with the molecules that are concentrated and immobilized on it. All of these components communicate with each other and with the neoplastic cells to contribute to the aberrant tumor organ. Factors elaborated by tumors cause dramatic increases in inflammatory myeloid cells in the microenvironment of the primary tumor as well as in distant sites upon the malignant conversion of the tumor cells. These myeloid cells modulate the tumor ecology and regulate metastatic take, altering vascular permeability and responses to chemotherapy. The dynamic interplay of tumor cells and host cells responding to the tumor in the microenvironment contribute to tumor evolution, metastasis and evasion of therapeutic responses. Supported by grants from the National Cancer Institute. Chou, J., J.H. Lin, A. Brenot, J.-w. Kim, S. Provot &amp; Z. Werb (2013). GATA3 suppresses metastasis and modulates the tumor microenvironment by regulating miR-29 expression. Nat. Cell Biol. 15: 201-213. [2013 Jan 27, PMCID: PMC3660859. Chou, J., P. Shahi &amp; Z. Werb (2013). MicroRNA-mediated regulation of the tumor microenvironment. Cell Cycle. In press. Egeblad, M., A. J. Ewald, H. A. Askautrud, B. E. 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Coussens (2010). Stromal regulation of vessel stability by MMP9 and TGFβ. Dis. Model. Mech. 3: 317-332. PMCID: PMC20223936. Citation Format: Amy Jo Casbon, Marja Lohela, Vicki Plaks, Zena Werb. How tumors regulate their microenvironment in primary sites and metastasis. [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 IA24.