REGULATION OF CELLS BY MATRIX AND HORMONES

我们的实验室致力于化学和生物学研究 细胞外基质，以及基质和激素之间的协同作用 调节细胞生理学。多年来，我们一直是 开发必要的技术来研究基质和 激素在分化哺乳动物基因表达调控中的作用 上皮样细胞，肝细胞，以及在它们的肿瘤对应物中， 肝癌。这些技术允许我们培养正常的肝细胞 或肝癌，所以它们要么以最快的速度生长，要么以较低的速度生长 肝脏特异性功能水平或维持为非生长细胞 具有更高水平的肝脏特异性功能。这些技术包括 使用无血清、激素限定的培养液和提取物的底物 含有细胞外基质，称为生物基质。目前，我们 正在对生物基质进行化学解剖以确定哪些分子是 负责其生物活性，并利用这些信息形成 由已定义和提纯的基质成分组成的底物。首字母 研究已经单独使用了已知的矩阵成分，并且在各种情况下 组合。在对这些培养物及其成分进行优化之后， 我们将把生物基质提取物作为 其他具有生物活性的基质成分的提纯。这个 这个项目涉及生物和化学技术，所以我们有 融合了L.Rosenberg博士的专业知识，他在提纯方面有经验 E·J·米勒博士对蛋白多糖进行了表征，他在 胶原蛋白的纯化和性质，以及L.Reid博士，一种细胞 在培养分化的哺乳动物方面有专长的生物学家 上皮细胞。这家合资企业应该会最大限度地增加 成功开发用于生长和/或生长的限定基质基质 上皮细胞的分化。(A)

Our laboratories are concerned with the chemistry and biology of extracellular matrix and with the synergies between matrix and hormones in regulating cellular physiology. For a number of years we have been developing the technologies necessary to study the roles of matrix and hormones in regulating gene expression in a differentiated mammalian epithelioid cell, the hepatocytes, and in their neoplastic counterparts, the hepatomas. These technologies permit us to culture normal hepatocytes or hepatomas so that they either grow at maximal rates and with lower levels of liver-specific functions or are maintained as non-growing cells with higher levels of liver-specific functions. The technologies include the use of serum-free, hormonally defined media and substrata of extracts containing extracellular matrix referred to as biomatrix. At present, we are chemically dissecting the biomatrix to ascertain which molecules are responsible for its biological activity and using the information to form substrata composed of defined and purified matrix components. The initial studies have utilized known matrix components alone and in various combinations. After optimization of these cultures with their components, we will turn to the biomatrix extracts as a source material for the purification of other matrix components with biological activity. The project involves the technologies of both biology and chemistry, so we have fused the expertise of Dr. L. Rosenberg, who has experience in purifying and characterizing proteoglycans, Dr. E. J. Miller, who has experience in purification and characterization of collagens, and Dr. L. Reid, a cell biologist who has expertise in culturing differentiated mammalian epithelial cells. This joint venture should maximize the chances of success in developing defined matrix substrata for growth and/or differentiation of epithelial cells. (A)