Abstract
Abstract Most clinical therapeutics used to date depend on specific targeting of cellular components to treat cancers. However, the environment outside the tumor cell is also critical since it may provide new targets to treat malignant and resistant cancers, independent of the tumor. We aim to advance the understanding of the early stages of cancer, prior to metastasis by determining the role of a non-fibrillar collagen (Type XV) and its interactions with the tumor stroma and extracellular environment. Type XV collagen (COLXV) is found in basement membrane zones where it assumes a pretzel-like structure but unlike the majority of fibrillar collagens does not form tight lattice networks surrounding the cell. Loss of COLXV during progression of aggressive cancers (including breast, pancreas, and ovarian carcinomas and melanomas) precedes basement membrane invasion and metastasis. Moreover, the loss of COLXV from the distal side of basement membrane zones and the resulting deficit in its interactions with other proteins may determine its specific function in tumor progression and eventual metastasis. In this context we have identified critical collagen-binding cell surface receptors on the tumor cell, which interact with COLXV and appear to mediate its functions. These receptors have also been reported to show altered signaling in cancer. We previously showed that over-expression of COLXV in cervical cancer cells alters the growth properties of these cells both in vitro and in vivo, and showed that type XV collagen is a dose-dependent suppressor of tumorigenicity in vivo. We now show that over-expression of COLXV inhibits epithelial to mesenchymal transition (EMT) in vitro and has a dramatic effect on the associated signaling events. We are now further investigating the mechanisms of tumor/stroma crosstalk that are impacted by COLXV and subsequently by its depletion. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5174. doi:1538-7445.AM2012-5174
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