Abstract 1631: Cav1 is a key mediator of tumor-stromal interactions in melanoma.

Abstract Several lines of experimental evidence have demonstrated the importance of the tumor microenvironment in controlling melanoma tumor growth and melanoma metastasis. Caveolin1 (Cav1), the main structural component of the plasma membrane microdomains termed Caveolae, is emerging as an important signaling molecule in the stroma of several tumor types. However, Cav1’s function in the melanoma microenvironment of primary tumors and of metastasis remains largely unexplored. Here, we devise various experimental approaches to elucidate the function of stromal Cav1 in the development of melanoma in mice. We show that loss of Cav1 (but not Cav2) in mice promotes the growth of orthotopically implanted melanoma cells. We use cocultures of fibroblasts and melanoma cells coupled with cytokine analysis to identify various Cav1 regulated factors that function in a paracrine fashion in melanoma. Cav1KO fibroblasts secrete increased amount of ShhN, bFGF, and MMP2/3, cytokines known to promote proliferation of melanoma cells and remodeling of the tumor stroma during melanomagenesis. Intradermal xenografts of fibroblasts and melanoma cells (5:1 ratios) confirmed the tumor promoting role of fibroblasts lacking Cav1. Interestingly, constitutive inhibition of the Shh pathway in melanoma cells reverses the growth and tumor-promoting effects of Cav1KO fibroblasts in co-culture or co-injection experiments suggesting a Cav1 mediated Shh heterotypic interaction between fibroblasts and melanoma cells. In summary, these studies reveal previously undefined functions for Cav1 in the melanoma microenvironment that could potentially be targeted for therapy. Citation Format: Casey Trimmer, Franco Capozza. Cav1 is a key mediator of tumor-stromal interactions in melanoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1631. doi:10.1158/1538-7445.AM2013-1631 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.