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Elucidating The Role Of Adhesion Factors In Circulating Tumor Cell Clustering For Breast Cancer Metastasis And Venous Thromboembolism

667 words - 3 pages

A. Background: Breast cancer has now become a disease which, in most cases, is easily treatable if detected early or non-aggressive. However, the major cause of death for patients with breast cancer is metastasis of tumor cells from the primary tumor to secondary sites throughout the body. Determining the hallmarks to differentiate aggressive tumors versus non-aggressive tumors will not only in how clinicians choose to initially treat the patients, but also could potentially be used as therapeutic targets to specifically target metastatic tumor cells. Determining the factors involved in allowing circulating tumor cells to adhere to each other and to blood vessel walls could lead to improved treatment options for patients with metastatic breast cancer. However, paclitaxel has been shown to be ineffective for treatment of metastatic breast cancer. Proteins associated with the pericentriolar material (PCM) have been recently implicated as having major roles in microtubule nucleation and localization of some of these proteins has been shown to have changed in breast tumor cells versus normal cells. Thus the study of the proteins involved in the initial event of microtubule nucleation and the steps immediately following nucleation and how their interactions deviate from normal cellular activity could reveal crucial molecular biomarkers to treat metastatic breast cancer.

B. Rationale: We seek to study the process of microtubule nucleation in various breast tumor cell lines of diverse metastatic potential and understand the role of abnormal microtubule nucleation in breast cancer metastasis. Preliminary studies from our lab have shown a dissimilar staining pattern by immunofluorescence in the major microtubule nucleating protein, γ-tubulin, as compared with normal cells. Furthermore, other proteins involved in microtubule nucleation, anchoring, and localization have been shown to have differential expression in increasingly metastatic breast cancer cell lines.

C. Objectives: 1) Does the incidence of aberrant microtubule nucleation increase in breast tumor cell lines? Recent preliminary data in our lab has confirmed the occurrence of microtubule nucleation...

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