Nicolson G L
Department of Tumor Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Oncol Res. 1992;4(10):389-99.
The successful growth of metastatic tumor cells is due to their responses to local paracrine growth factors and inhibitors and their production and responses to autocrine growth factors. 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 affecting metastatic cells. At later stages of metastatic progression, where widespread dissemination to various tissues and organs occurs, autocrine growth mechanisms may dominate the growth signals affecting metastatic cells. The progression of malignant cells to completely autonomous (acrine) states can ultimately occur, and at this stage of metastatic progression cell growth can be completely independent of growth factors or inhibitors. Various strategies have been developed to treat cancer that are based on the responses of malignant cells to growth factor or inhibitor analogs, anti-receptor antibodies, or antibody- or growth factor-toxin conjugates. Since the responses and expression of growth factor receptors can change during malignant progression, the development of cancer treatments using analogs of specific growth inhibitors or antagonists of growth factors, such as monoclonal antibodies or other agents, to block growth signaling mechanisms may only be useful at the early stages of malignant cancer progression before widespread metastasis of acrine cells occurs.
转移性肿瘤细胞的成功生长归因于它们对局部旁分泌生长因子和抑制剂的反应，以及它们对自分泌生长因子的产生和反应。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在特定部位生长，这表明旁分泌生长机制可能主导影响转移细胞的生长信号。在转移进展的后期阶段，肿瘤细胞广泛扩散到各种组织和器官，自分泌生长机制可能主导影响转移细胞的生长信号。恶性细胞最终可能发展到完全自主（自分泌）状态，在此转移进展阶段，细胞生长可以完全独立于生长因子或抑制剂。已经开发出各种基于恶性细胞对生长因子或抑制剂类似物、抗受体抗体或抗体 - 生长因子 - 毒素偶联物的反应来治疗癌症的策略。由于生长因子受体的反应和表达在恶性进展过程中可能发生变化，因此使用特定生长抑制剂类似物或生长因子拮抗剂（如单克隆抗体或其他药物）来阻断生长信号机制的癌症治疗方法可能仅在恶性肿瘤进展的早期阶段有用，即在自分泌细胞广泛转移之前。
