Arvelo Francisco, Sojo Felipe, Cotte Carlos
Centro de Biociencias, Fundación Instituto de Estudios Avanzado [IDEA], Caracas 1015-A, Venezuela, Apartado 17606, Caracas 1015-A, Venezuela; Laboratorio de Cultivo de Tejidos y Biología de Tumores, Instituto de Biología Experimental, Universidad Central de Venezuela, Apartado 47114, Caracas, 1041-A, Venezuela.
Laboratorio de Cultivo de Tejidos y Biología de Tumores, Instituto de Biología Experimental, Universidad Central de Venezuela, Apartado 47114, Caracas, 1041-A, Venezuela.
Ecancermedicalscience. 2016 Jan 29;10:617. doi: 10.3332/ecancer.2016.617. eCollection 2016.
The two biological mechanisms that determine types of malignancy are infiltration and metastasis, for which tumour microenvironment plays a key role in developing and establishing the morphology, growth and invasiveness of a malignancy. The microenvironment is formed by complex tissue containing the extracellular matrix, tumour and non-tumour cells, a signalling network of cytokines, chemokines, growth factors, and proteases that control autocrine and paracrine communication among individual cells, facilitating tumour progression. During the development of the primary tumour, the tumour stroma and continuous genetic changes within the cells makes it possible for them to migrate, having to count on a pre-metastatic niche receptor that allows the tumour's survival and distant growth. These niches are induced by factors produced by the primary tumour; if it is eradicated, the active niches become responsible for activating the latent disseminated cells. Due to the importance of these mechanisms, the strategies that develop tumour cells during tumour progression and the way in which the microenvironment influences the formation of metastasis are reviewed. It also suggests that the metastatic niche can be an ideal target for new treatments that make controlling metastasis possible.
决定恶性肿瘤类型的两种生物学机制是浸润和转移,肿瘤微环境在恶性肿瘤的形态形成、生长和侵袭性发展及确立过程中起着关键作用。微环境由包含细胞外基质、肿瘤细胞和非肿瘤细胞的复杂组织构成,是一个由细胞因子、趋化因子、生长因子和蛋白酶组成的信号网络,该网络控制着单个细胞之间的自分泌和旁分泌通讯,促进肿瘤进展。在原发性肿瘤发展过程中,肿瘤基质以及细胞内持续的基因变化使肿瘤细胞能够迁移,这需要依赖一种转移前生态位受体,该受体能使肿瘤存活并在远处生长。这些生态位由原发性肿瘤产生的因子诱导形成;如果原发性肿瘤被根除,活跃的生态位就会激活潜伏的播散细胞。鉴于这些机制的重要性,本文综述了肿瘤细胞在肿瘤进展过程中所形成的策略以及微环境影响转移形成的方式。文章还指出,转移生态位可能是实现转移控制的新治疗方法的理想靶点。