Modulation of Anaplastic Lymphoma Kinase Upon Tumor-Stroma Interaction and Its Implications for Tumor Growth and Metastasis in Breast Cancer
Annual rept. 1 Sep 2003-31 Aug 2004
GEORGETOWN UNIV WASHINGTON DC MEDICAL CENTER
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Induction of neovascularization is needed for a growing tumor as well as for its metastasis. Angiogenic and growth promoting factors like Pleiotrophin PTN act on endothelial and epithelial cells and on fibroblasts. We identified the receptor for PTN as anaplastic lymphoma kinase ALK. In individual tissues the presence of ALK is elevated in tumor stroma endothelium while adjacent normal tissue lacked ALK. In cultured endothelial cells or human fibroblasts ALK is upregulated in response to supernatants from human breast cancer cells. Our hypothesis is that ALK from stromal cells., upregulated in response to factors from tumor cells, constitutes as marker and a potential therapeutic target in breast cancer. We will investigate the specificity of ALK modulation in tumor stroma versus normal endothelium in response to growth factors and breast cancer cell lines supernatants. Also, we will determine the functional effects of the differences in ALK signaling and uncover the differences in drug sensitivity in cells that have an increased ALK level versus untreated. We expect a lowering of the effective dose thus lowering the side effects of these drugs. The completion of the study will translate in establishing ALK as a new target for the breast metastatic cancer therapy.
- Medicine and Medical Research