Abstract

Abstract Cancer cell metastasis is one of the most critical steps in tumor development and is responsible for more than 80% of cancer related deaths. The cell adhesion molecule CD44 promotes cancer cell motility and metastasis. Despite this knowledge, the molecular mechanism through which CD44 promotes tumor development and cell metastasis is still unclear. The CD146 (MUC 18), another member of the cell adhesion molecules family, first identified in highly metastatic melanomas. The absence of CD146 in normal melanocytes and its high expression in melanomas suggests its tumor promoting actions. However, CD146 appears to suppress breast tumor progression. Furthermore, despite the association between CD146 expression and development of melanoma, the expression patterns and the role of CD146 in normal and metastatic breast tissues are still controversial. In a pilot study, we have identified CD146 as a potential downstream target of CD44-signaling in the MDA-435 breast cancer cell line, using subtractive hybridization and northern blot analyses. In this paper we provide evidence that CD146 is a downstream target for CD44, in a way that CD146 expression is regulated according to tumor microenvironment. Finally, this study demonstrates a new role for CD44 in regulating neovascularization and promoting cancer cell transmigration of blood vessels via CD146. Citation Format: Allal Ouhtit, Mohamed Abdraboh, Andrew D. Hollenbach, Ishita Gupta, Somya Shanmuganathan, Hamad Al Riyami, Youssef Errami, Yahya Al Farsi, Madhwa HG Raj. CD146 is a novel target of CD44-signaling mediating breast tumor invasion. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr A71.

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