Vaidya Kedar S, Welch Danny R
Department of Pathology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
J Mammary Gland Biol Neoplasia. 2007 Sep;12(2-3):175-90. doi: 10.1007/s10911-007-9049-1.
Metastasis remains the most deadly aspect of cancer and still evades direct treatment. Clinically and experimentally, primary tumor development and metastasis are distinct processes-locally growing tumors can progress without the development of metastases. The discovery of endogenous molecules that exclusively inhibit metastasis suggests that metastasis is an amenable therapeutic target. By definition, metastasis suppressors inhibit metastasis without inhibiting tumorigenicity and are thus distinct from tumor suppressors. As the biology underlying functional mechanisms of metastasis suppressors becomes clearer, it is evident that metastasis suppressors could be harnessed as direct drug targets, prognostic markers, and to understand the fundamental biology of the metastatic process. Metastasis suppressors vary widely in their cellular localization: they are found in every cellular compartment and some are secreted. In general, metastasis suppressors appear to regulate selectively how cells respond to exogenous signals, by affecting signaling cascades which regulate downstream gene expression. This review briefly summarizes current functional and biochemical data on metastasis suppressors implicated in breast cancer. We also present a schematic integrating known mechanisms for these metastasis suppressors highlighting potential targets for therapeutic intervention.
转移仍然是癌症最致命的方面，并且仍然难以直接治疗。在临床和实验中，原发性肿瘤的发展和转移是不同的过程——局部生长的肿瘤可以在不发生转移的情况下进展。专门抑制转移的内源性分子的发现表明转移是一个可治疗的靶点。根据定义，转移抑制因子抑制转移而不抑制肿瘤发生，因此与肿瘤抑制因子不同。随着转移抑制因子功能机制的生物学基础变得更加清晰，可以明显看出转移抑制因子可作为直接的药物靶点、预后标志物，并有助于理解转移过程的基本生物学。转移抑制因子在细胞定位上差异很大：它们存在于每个细胞区室中，有些是分泌型的。一般来说，转移抑制因子似乎通过影响调节下游基因表达的信号级联反应，选择性地调节细胞对外源信号的反应。本综述简要总结了目前与乳腺癌相关的转移抑制因子的功能和生化数据。我们还展示了一个示意图，整合了这些转移抑制因子的已知机制，突出了治疗干预的潜在靶点。
