Silletti S, Yao J P, Pienta K J, Raz A
Metastasis Research Program, Michigan Cancer Foundation, Detroit 48201, USA.
Int J Cancer. 1995 Sep 27;63(1):100-5. doi: 10.1002/ijc.2910630118.
Tumor cell migration and proliferation in new organ environments are critical steps in cancer progression and can be modulated by tumor- and host-secreted molecules. Autocrine motility factor (AMF) is a tumor-secreted cytokine which regulates growth and motility by a receptor-mediated pathway. The AMF receptor, a 78-kDa cell surface glycoprotein (gp78), is regulated by cell contact in normal fibroblastic and bladder cells; however, this mechanism is disrupted during tumor progression. A prostatic carcinoma cell line which is low- to non-metastatic in nude mice (PC-3) and a derived metastatic variant (PC-3M) were examined to determine if gp78 cell density regulation is involved in prostate cancer progression. Both cell lines expressed gp78 and, although the basal migration of the parental PC-3 cells was higher than that of the metastatic variant, only the PC-3M cells were capable of responding to tumor-derived AMF with increased motility. Furthermore, these cells exhibited differential patterns of wound closure in an experimental system whereby the low-metastatic PC-3 cells migrated primarily along the wound edge while individual high-metastatic PC-3M cells entered the cell-free wound area directly. Cell surface gp78 distribution distinguished the cell populations with a markedly concentrated display of gp78 in polarized capped regions on the surface of the metastatic cells. Cell-cell contact down-regulated gp78 expression in the parental, but not the metastatic, cells, and mitogenic responses to exogenous AMF differed between these cell lines as well. In this model, metastasis appears to be associated with aberrant regulation of gp78 expression and distribution, coupled with enhanced exploitation of AMF's locomotory and proliferative effects.
肿瘤细胞在新的器官环境中的迁移和增殖是癌症进展的关键步骤，并且可受到肿瘤和宿主分泌分子的调节。自分泌运动因子（AMF）是一种肿瘤分泌的细胞因子，它通过受体介导的途径调节生长和运动。AMF受体是一种78kDa的细胞表面糖蛋白（gp78），在正常成纤维细胞和膀胱细胞中受细胞接触调节；然而，在肿瘤进展过程中这种机制被破坏。研究了一种在裸鼠中低转移至不转移的前列腺癌细胞系（PC-3）及其衍生的转移变体（PC-3M），以确定gp78细胞密度调节是否参与前列腺癌进展。两种细胞系均表达gp78，尽管亲本PC-3细胞的基础迁移率高于转移变体，但只有PC-3M细胞能够对肿瘤来源的AMF作出反应，表现出运动性增加。此外，在一个实验系统中，这些细胞表现出不同的伤口愈合模式，低转移的PC-3细胞主要沿伤口边缘迁移，而单个高转移的PC-3M细胞直接进入无细胞的伤口区域。细胞表面gp78的分布区分了细胞群体，gp78在转移细胞表面的极化帽状区域明显集中显示。细胞间接触下调了亲本细胞而非转移细胞中gp78的表达，并且这些细胞系对外源AMF的促有丝分裂反应也不同。在这个模型中，转移似乎与gp78表达和分布的异常调节有关，同时伴随着对AMF运动和增殖作用的增强利用。
