Colorectal carcinoma is the second greatest cause of death in the United States among all types of neoplasms. The mortality of this disease is the result of regional and systemic metastasis. Although a variety of biological and biochemical properties that determine the metastatic capability of mammary carcinoma, lung carcinoma, melanoma and lymphosarcoma have been elucidated in experimental animal model systems, little is known about the mechanisms and determinants of colorectal carcinoma metastasis in cancer patients because of the lack of a suitable experimental model. Since the most commonly use therapeutic procedure for colorectal carcinoma is surgery, a relatively large number of fresh tumor specimens, together with comprehensive patient records, are available at the M.D. Anderson Hospital. In the proposed project, we will develop a rapid, micro-scale analytical method for the examination of biochemically definable cell surface properties in colorectal cancer which have been proposed to be related to metastatic behavior of tumor cells in experimental systems. These include various types of cell surface glycoproteins, extracellular proteoglycans, and hydrolytic enzymes responsible for the destruction of tissue integrity, such as heparanase and type IV collagenase. When relatively large tumor tissues are available, the targeted molecules will be purified from them. Antibodies (monoclonal or polyclonal) against the e molecules together with specific histochemical agents for glycoconjugates will be histochemically utilized in order to examine localization and intercellular heterogeneity in the distribution of the molecules. The results of this proposed study will provide new information concerning the cell surface properties of the highly metastatic subpopulation of primary colorectal tumors. The development of this technology could serve as a useful tool for prognosticating matastasis of this disease. Also, the results may be a basis for the study of specific antimentastatic therapy which can be applied in concert with other therapeutic modalities of the primary tumor.
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