MINORITY PREDOCTORAL FELLOWSHIP PROGRAM

少数族裔博士前奖学金计划

• 批准号: 2545406
• 负责人: BERTHA A PELAYO
• 金额: $ 2.01万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-10-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2545406
• 关键词: enzyme activity; extracellular matrix; melanoma; metastasis; minority health professional; neoplastic cell

Degradation of the extracellular matrix in normal tissue surrounding a tumor leads to invasion and ultimately metastasis. It is this process that makes cancers malignant. Previous studies have shown that the proteolytic enzymes, matrix metalloproteinases (MMPs) and plasminogen activators (PAs), as well as their inhibitors, tissue inhibitors of metalloproteinases (TIMPs) and plasminogen activator inhibitors (PAIs), are involved in the degradation of the extracellular matrix. Preliminary data suggest that degradation of the extracellular matrix is controlled by tumor cell-adjacent cell modulation of these extracellular matrix degrading enzymes and their inhibitors. We will specifically examine this interaction by 1) identifying and quantifying the secretion of MMPs, PAs, TIMPs and PAIs by murine syngeneic normal dermal keratinocytes, dermal fibroblasts, melanocytes (Mel-ab), the poorly invasive and poorly metastatic B16 melanoma and the highly invasive and highly metastatic BL6 variant; 2) comparing secretion and activation of MMPs and PAs and comparing secretion of these inhibitors in cocultures of keratinocytes and fibroblasts with melanocytes, B16 and BL6 melanoma cells with the individual cell cultures and 3) identifying components that influence the balance between activated MMPs PAs and their inhibitors that lead to invasion and eventually metastasis.

围绕正常组织的细胞外基质的降解 肿瘤导致侵袭并最终转移。这是这个过程 这会使癌症恶性。以前的研究表明 蛋白水解酶，基质金属蛋白酶（MMP）和纤溶酶原 激活剂（PA）及其抑制剂，组织抑制剂 金属蛋白酶（TIMP）和纤溶酶原激活剂抑制剂（PAIS），，， 参与细胞外基质的降解。初步的 数据表明，控制细胞外基质的降解 通过这些细胞外基质的肿瘤细胞粘附细胞调节 降解酶及其抑制剂。我们将专门研究这个 通过1）识别和量化MMP的分泌PA， Timps and pais由鼠类合成正常皮肤角质形成细胞，真皮 成纤维细胞，黑素细胞（MEL-AB），侵入性差 转移性B16黑色素瘤和高度侵入性和高度转移性BL6 变体2）比较MMP和PA的分泌和激活以及 比较角质形成细胞共培养中这些抑制剂的分泌 与黑色素细胞，B16和BL6黑色素瘤细胞的成纤维细胞与 单个细胞培养和3）识别影响的组成部分 在激活的MMP PA及其抑制剂之间的平衡 入侵和最终转移。