Prostate cancer is the most common cancer diagnosed in American men and remains incurable once it has metastasized. Many stages of the metastatic cascade involve cellular interactions mediated by cell surface components such as carbohydrate-binding proteins, which include galactoside binding lectins (galectins). Specifically, tumor cell-endothelial cell adhesion and tumor cell-tumor cell emboli are known to be mediated in part by lectin-carbohydrate interactions. We have demonstrated that oral intake of a pH-modified citrus pectin (modified citrus pectin), a non-cytotoxic natural complex carbohydrate fiber found in citrus fruits and rich in galactose residues, acted as a potent inhibitor of spontaneous prostate carcinoma metastasis in the rat and believe that modified citrus pectin could potentially be developed for clinical antimetastasis therapy as well as metastasis prevention (JNCI, In Press, 1995). Modified citrus pectin inhibits the adhesion of both rat and human prostate cancer cells to endothelial cells and also inhibits tumor cell - tumor cell interactions in vitro but does not affect the growth of cancer cells in vitro or in vivo. We hypothesize, therefore, that modified citrus pectin acts as an """"""""anti-adhesive"""""""" agent. Anti-adhesive agents, i.e., agents which disrupt cell-cell adhesion or cell-extracellular matrix interactions, have been proposed as potential anti-cancer drugs but have received little study. We propose to define the mechanism of action of modified citrus pectin. Specifically, we will (1): Define the active, stereospecific, carbohydrate moiety of modified citrus pectin which confers anti-adhesive activity. (2) Identify the cell surface components which bind to modified citrus pectin. (3) Test the ability of modified citrus pectin to inhibit metastasis of human prostate cancer cells utilizing in vivo models. The results of these studies will further define the ability of the stereospecific carbohydrate moiety of modified citrus pectin to inhibit human prostate cancer metastasis. We believe that an inhibitor of metastasis such as modified citrus pectin could have great clinical impact. Patients at high risk for continued tumor growth and subsequent metastasis, e.g., patients with positive margins at radical prostatectomy but no clinical evidence of disease, may benefit from a nontoxic agent which prevented further spread of tumor.
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