POLARIZED SECRETION BY PROSTATIC CELLS

体内前列腺上皮细胞在结构和功能上都是极化的。 功能上。 然而，对极化上皮细胞的作用的研究 细胞分泌物在调节正常和异常生长中的作用， 由于缺乏合适的实验系统，初步 这项研究计划中的研究表明，正常和肿瘤 前列腺上皮细胞可以作为极化汇合上皮细胞生长， 以更好地模仿其在两室培养室中的 in vivo体内counterparts对应.此外，顶面和底面的 前列腺上皮细胞在双腔室中生长， 独立监测和实验修改，从而允许 研究这些细胞的极化分泌物在 正常和恶性生长的生理学。特别是，这一目标 研究建议是1/进一步发展两院制培养室 系统，从而促进调查2/旁分泌的作用 上皮细胞和基质细胞之间的相互作用， 正常和异常生长，和3/测试的假设， 转变可能与极性或极性的丧失有关。 逆转或基底外侧方向的蛋白质分泌。的确， 上皮细胞转化与形态学改变有关， 前列腺极性丧失（间变性）多年。在这 背景下，致癌转化和 蛋白酶分泌的极性逆转可能在压倒性的 基底膜的细胞外基质， 增强细胞外基质降解， 转移此外，一种与地球的极性反转有关的 蛋白质分泌可能解释了 前列腺增生患者血清前列腺酸性磷酸酶的测定 癌 这些实验应该提供重要的新信息 前列腺生长的旁分泌调节机制。 其次，这些实验可能证明了一种与 蛋白质分泌的极性逆转，以及这种转变是如何 相关现象可能促进转移，并解释滴度升高 前列腺增生患者血清前列腺酸性磷酸酶的测定 癌因此，本研究的长期目标 建议是阐明参与的机制， 调节正常和异常的前列腺生长，因此， 操纵，以修改和控制这种异常生长。

Prostatic epithelial cells in vivo are polarized both structurally and functionally. However, investigation of the role of polarized epithelial cell secretions in the regulation of normal and aberrant growth has been hindered by a lack of an appropriate experimental system. Preliminary studies in this research proposal demonstrate that normal and neoplastic prostatic epithelial cells can be, grown as polarized confluent epithelial sheets in bicameral culture chambers in a manner that better mimics their in vivo counterparts. In addition, the apical and basal surfaces of the prostatic epithelial cells grown in the bicameral chambers can bc independently monitored and experimentally modified, thereby allowing investigation of the role of polarized secretion from these cells in the physiology of normal and malignant growth. In particular, the aims of this research proposal are 1/ to further develop the bicameral culture chamber system thereby facilitating investigation of 2/ the role of paracrine interactions between epithelial cells and stromal cells in the regulation of normal and aberrant growth, and 3/ to test the hypothesis that oncogenic transformation may be associated with a loss of polarity, or polarity reversal or protein secretion in a basolateral direction. Indeed, epithelial cell transformation has been associated with a morphological loss of polarity (anaplasia) in the prostate for many years. In this context, a functional association between oncogenic transformation and polarity reversal of protease secretion could play a role in overwhelming the extracellular matrix of the underlying basement membrane, thereby enhancing extracellular matrix degradation that has been associated with metastasis. In addition, a transformation associated polarity reversal of protein secretion could potentially explain the elevated titers of prostatic acid phosphatase in the serum of patients with prostatic carcinomas. These experiments should provide significant new information on the mechanisms involved in the paracrine regulation of prostatic growth. Secondly, these experiments may demonstrate a transformation associated polarity reversal of protein secretion, and how such a transformation associated phenomena may facilitate metastasis, and explain elevated titers of prostatic acid phosphatase in the serum of patients with prostatic carcinomas. In this context, the long term objectives of this research proposal are to elucidate the mechanisms which are involved in the regulation of normal and aberrant prostatic growth, and therefore, may be manipulated in order to modify and control such aberrant growth.