Nicolson G L
Department of Tumor Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Cancer Metastasis Rev. 1993 Sep;12(3-4):325-43. doi: 10.1007/BF00665961.
Once metastatic cells successfully seed at distant sites, their clinical detection and danger to the host are dependent on growth to form gross metastases. Metastatic tumor cells proliferate in response to local paracrine growth factors and inhibitors, and their growth also depends on production and responses to autocrine growth factors. A major organ-derived (paracrine) growth factor from lung tissue-conditioned medium has been isolated that differentially stimulates the growth of cells metastatic to brain or lung. Characterization of this mitogen demonstrated that it is a transferrin or a transferrin-like glycoprotein. Furthermore, antibodies to transferrin can remove significant growth activity from lung tissue-conditioned medium. Cells that are metastatic to brain or lung express greater numbers of transferrin receptors on their surfaces than cells that are poorly metastatic or metastatic to liver. Growth responses of metastatic cells and organ preferences of colonization appear to change during progression to more malignant states. At early stages of metastatic progression there is a tendency for many common malignancies to metastasize and grow preferentially at particular sites, suggesting that paracrine growth mechanisms may dominate the growth signals at this stage of progression. In contrast, at later stages of metastatic progression widespread dissemination to various tissues and organs occurs, and autocrine growth mechanisms may dominate the growth responses of metastatic cells. Ultimately, the progression of malignant cells to completely autonomous (acrine) states can occur, and at this stage of metastatic progression cell growth may be completely independent of autocrine and paracrine growth factors or inhibitors.
一旦转移细胞成功在远处位点着床，它们的临床检测及对宿主的危害就取决于生长形成肉眼可见的转移灶。转移瘤细胞会响应局部旁分泌生长因子和抑制剂而增殖，其生长还依赖于自分泌生长因子的产生及对其的反应。一种从肺组织条件培养基中分离出的主要器官来源（旁分泌）生长因子，能差异性地刺激转移至脑或肺的细胞生长。对这种有丝分裂原的特性分析表明，它是一种转铁蛋白或转铁蛋白样糖蛋白。此外，抗转铁蛋白抗体可去除肺组织条件培养基中的显著生长活性。转移至脑或肺的细胞表面表达的转铁蛋白受体数量，比转移能力差或转移至肝脏的细胞更多。转移细胞的生长反应和定植的器官偏好似乎在向更恶性状态进展的过程中会发生变化。在转移进展的早期阶段，许多常见恶性肿瘤倾向于优先转移并生长于特定部位，这表明旁分泌生长机制可能在这一进展阶段主导生长信号。相比之下，在转移进展的后期阶段，会出现广泛扩散至各种组织和器官的情况，自分泌生长机制可能主导转移细胞的生长反应。最终，恶性细胞可能会发展到完全自主（自分泌）状态，在转移进展的这个阶段，细胞生长可能完全独立于自分泌和旁分泌生长因子或抑制剂。
