Promotion of Metastatic Processes by Laminin and Laminin Peptides

研究是为了定义这些机制。 参与肿瘤的生长和转移并开发新的动物 人类癌症的模型。我们发现有一个地下室 膜提取物(Matrigel)与人肿瘤预混 细胞(在老鼠体内不能很好地生长)会促进它们的发生和 成长。我们已经能够培养出新的高度差异化的 从小鼠体内生长的肿瘤中获得的人类肿瘤细胞系包括 某些结肠细胞系。层粘连蛋白，一种主要的基底膜 成分，已被发现促进恶性表型。 层粘连蛋白贴壁细胞比 非贴壁细胞或亲本细胞。各种生物活性 层粘连蛋白衍生的合成肽已经被鉴定。一, YIGSR(酪氨酸-甘氨酸-精氨酸)可减少肿瘤生长、转移和 血管生成，而IKVAV则增强这些活性。另一个 多肽LQVQLSIR增加转移，但机制不是 还没有被定义。我们的目标是定义分子机制 参与肿瘤的生长和转移。我们的方法是(1) 选择并分离高度恶性的细胞，(2)定义其细胞 层粘连蛋白受体，(3)识别层粘连蛋白上的额外序列 哪些促进或减少了恶性表型，(4)识别 与恶性肿瘤有关的基因和(5)定义骨骼中的分子 负责前列腺癌和乳腺癌的器官特异性转移。 我们使用了几个模型，包括B16F10黑色素瘤细胞， 乳腺、前列腺和唾液腺肿瘤细胞。我们希望定义 参与转移的调节事件和开发治疗方法 和诊断试剂。

Studies are conducted to define the mechanisms involved in tumor growth and metastasis and to develop new animal models of human cancers. We have found that a basement membrane extract (Matrigel) when premixed with human tumor cells (which do not grow well in mice) promotes their incidence and growth. We have been able to culture new highly differentiated human tumor cell lines from the tumors grown in mice including certain colon cell lines. Laminin, a major basement membrane component, has been found to promote the malignant phenotype. Laminin adherent cells are more malignant than either the non-adherent cells or the parental cells. Various biologically active laminin-derived synthetic peptides have been identified. One, YIGSR (tyr-ile-gly-ser-arg) reduces tumor growth, metastases, and angiogenesis whereas IKVAV increases these activities. Another peptide LQVQLSIR increases metastases but a mechanism has not yet been defined. Our goal is to define the molecular mechanisms involved in tumor growth and metastases. Our approach is to (1) select for and isolate highly malignant cells, (2) define their cellular laminin receptors, (3) identify additional sequences on laminin which promote or reduce the malignant phenotype, (4) identify genes involved in malignancy and (5) define molecules in bone responsible for prostate and breast cancerorgan-specific metastases. We work with several models including B16F10 melanoma cells, breast, prostate and salivary gland tumor cells. We hope to define regulatory events involved in metastases and develop therapeutic and diagnostic reagents.