GROWTH FACTORS AND HUMAN BLADDER CANCER

我们项目的长期目标是研究增长因素的作用 (GFS)及其受体在正常尿路上皮动态平衡中的作用 尿路上皮恶性病变的诱导和维持。膀胱的 上皮细胞处于永久沐浴在水池中的独特位置 天然的有丝分裂原，如表皮生长因子(EGF)， 它们在尿液中以很高的浓度排出， 具有生物活性的形式。尿路上皮细胞持续暴露于 这种物质可能导致持续的刺激，连续的细胞 分裂，并最终失去对增长的控制。因此，很可能是 对肿瘤和正常GFS的研究将阐明诱发和 维持移行细胞癌(TCC)。 我们正在：(1)检测正常和恶性患者的生长因子受体 移行上皮；(2)GFS的检测和特征 人类TCC(TCC-GFS)；和(3)评估TCC-GFS和其他GFS对 正常和恶性尿路上皮细胞，并选择其他细胞。最初的工作是 是在体外进行的。直接结合分析和竞争结合分析 放射性同位素标记的配体正被用于检测和定量 恶性和正常移行上皮细胞上的EGF受体 并研究它们的结合动力学。检测鲜肉中的受体 尿路上皮细胞及其在TCC上的分布与肿瘤分期、分级 和预后，放射自显影正在被利用。要素生产有 通过检测培养物中的生长刺激活动来记录 TCC细胞系在无血清培养液中生长的上清 产生细胞本身、其他移行细胞癌细胞和未转化的靶细胞。 已经执行了初步调整，并且至少有两个不同 一些刺激生长的活动已经被记录在案。我们计划 表征其他选定的化学和物理特性，这些特性将 请允许我们将这些“活动”与包括EGF在内的其他全球金融机构进行比较。 活性组分已被测试其刺激生长的能力 软琼脂中的正常成纤维细胞，这两个组分确实含有 转化能力。正常生长因子的生化性质 将测试(特别是EGF)和TCC-GFS，包括以下能力 刺激DNA合成，诱导鸟氨酸脱羧酶(ODC)活性，以及 改变目标细胞的多胺需求。此外，由于 最近商用的人类EGF，现在将有可能 与标准(小鼠)EGF对人的结合及作用的比较 尿路上皮和膀胱移行细胞癌靶标。(J)

Our project's long-term goal is to investigate the role of growth factors (GFs) and their receptors in normal urothelial homeostasis, and in the induction and maintenance of urothelial malignancy. The bladder's epithelium is in the unique position of being perpetually bathed by pools of naturally occurring mitogens such as epidermal growth factor (EGF), which are excreted in the urine in very high concentrations and in biologically active forms. The continuous exposure of urothelial cells to such substances may result in continuous stimulation, continuous cell division, and eventual loss of growth control. Thus, it is likely that the study of tumor and normal GFs will elucidate the processes which induce and maintain transitional cell carcinoma (TCC). We are: (1) examining growth factor receptors on normal and malignant transitional epithelium; (2) detecting and characterizing GFs produced by human TCC (TCC-GFs); and (3) assessing effects of TCC-GFs and other GFs on normal and malignant urothelium and selected other cells. Initial work is being performed in vitro. Direct and competitive binding assays with radioisotope-labeled ligands are being used to detect and quantitate receptors for EGF on malignant and normal transitional epithelial cells, and to study their binding kinetics. To examine the receptors on fresh urothelium and correlate their distribution on TCC with tumor stage, grade, and prognosis, autoradiography is being utilized. Factor production has been documented by detecting growth-stimulating activity in the culture supernates from TCC cell lines growing in serum-free medium, on the producing cells themselves, other TCC cells, and nontransformed targets. Preliminary sizing has already been performed, and at least two different fractions of growth-stimulating activity have been documented. We plan to characterize other selected chemical and physical properties which will allow us to compare these "activities" with other GFs, including EGF. Active fractions have been tested for their ability to stimulate the growth of normal fibroblasts in soft agar, and these two fractions do contain transforming ability. Biochemical properties of normal growth factors (particularly EGF) and TCC-GFs will be tested, including ability to stimulate DNA synthesis, induce ornithine decarboxylase (ODC) activity, and alter the polyamine requirements of target cells. In addition, because of the recent commercial availability of human EGF, it will now be possible to compare its binding and effects to that of standard (murine) EGF on human urothelial and TCC targets. (J)