INHIBITION OF HUMAN PROSTATE-CANCER METASTASIS BY MODIFIED CITRUS PECTIN

前列腺癌是美国男性最常见的癌症， 一旦转移就无法治愈。转移瘤的多个阶段 级联包括由细胞表面成分介导的细胞相互作用 例如碳水化合物结合蛋白，其包括半乳糖苷结合 凝集素(Galectins)。具体地说，肿瘤细胞与内皮细胞的黏附 而肿瘤细胞-肿瘤细胞栓子已知部分是通过 凝集素-碳水化合物的相互作用。我们已经证明了口服摄入量 一种pH修饰的柑橘果胶(改性柑橘果胶)，一种无细胞毒性的 天然复合碳水化合物纤维，存在于柑橘类水果中，富含 半乳糖残基，作为一种有效的自发性前列腺抑制剂 大鼠肿瘤转移模型，并认为改良的柑橘果胶 也可能被开发用于临床抗转移治疗 作为转移预防(JNCI，In Press，1995)。改性柑橘果胶 抑制大鼠和人前列腺癌细胞对 内皮细胞，也抑制肿瘤细胞与肿瘤细胞的相互作用 但不影响癌细胞在体外或体外的生长。 活着。因此，我们假设，改良的柑橘果胶起到了 “防粘剂”。防粘剂，即破坏 细胞-细胞黏附或细胞-细胞外基质相互作用 被认为是潜在的抗癌药物，但几乎没有得到研究。 我们建议对改性柑橘果胶的作用机理进行定义。 具体地说，我们将(1)：定义活性、立体特异性、碳水化合物 部分改性柑橘果胶，具有抗粘连活性。(2) 鉴定与改性柑橘果胶结合的细胞表面成分。 (3)检测改性柑橘果胶对小鼠肿瘤转移的抑制作用 利用体内模型研究人前列腺癌细胞。 这些研究的结果将进一步定义 改性柑橘果胶的立体专一性碳水化合物部分抑制作用 人前列腺癌转移。我们认为一种抑制药物的作用 转移，如改良的柑橘果胶，可能会有很大的临床价值 冲击力。肿瘤持续生长和随后的高风险患者 转移，例如，根治性前列腺切除术边缘呈阳性的患者 但没有疾病的临床证据，可能受益于无毒药物 从而防止了肿瘤的进一步扩散。

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.