Fazilaty Hassan, Gardaneh Mossa, Bahrami Tayyeb, Salmaninejad Arash, Behnam Babak
Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
Tumour Biol. 2013 Aug;34(4):2019-30. doi: 10.1007/s13277-013-0831-y. Epub 2013 May 19.
Metastatic colonization represents the final step of metastasis, and is the major cause of cancer mortality. Metastasis as an "inefficient" process requires the right population of tumor cells in a suitable microenvironment to form secondary tumors. Cancer stem cells are the only capable population of tumor cells to progress to overt metastasis. On the other hand, the occurrence of appropriate microenvironmental conditions within the target tissue would be critical for metastasis formation. Metastatic niche seems to be the specialized microenvironment to support tumor initiating cells at the distant organ. Master regulators not only determine cancer stem cell state, but also may have regulatory roles in metastatic niche elements. Meanwhile, both cancer stem cell and metastatic niche may function like two sides of the metastatic coin. Hypoxia inducible factors have multiple roles in regulation of both sides of this coin. TGF-β superfamily, also, have been considered as master regulators of epithelial to mesenchymal transition and metastasis and may play crucial roles in regulation of metastatic niche as well. In this regard, we hypothesize the presence of a possible emerging molecular pathway in the biological process of breast cancer metastasis. In this process, non-Smad TGF-β-induced metastasis connects cancer stem cell and metastatic niche formation through a central path, "Metastasis Pathway".
转移定植是转移的最后一步，也是癌症死亡的主要原因。转移作为一个“低效”过程，需要在合适的微环境中有合适的肿瘤细胞群体才能形成继发性肿瘤。癌症干细胞是唯一能够发展为明显转移的肿瘤细胞群体。另一方面，靶组织内合适的微环境条件的出现对于转移形成至关重要。转移小生境似乎是支持远处器官肿瘤起始细胞的特殊微环境。主要调节因子不仅决定癌症干细胞状态，而且可能在转移小生境元件中具有调节作用。同时，癌症干细胞和转移小生境可能就像转移这枚硬币的两面。缺氧诱导因子在这枚硬币的两面调节中都具有多种作用。TGF-β超家族也被认为是上皮-间质转化和转移的主要调节因子，并且可能在转移小生境的调节中也发挥关键作用。在这方面，我们假设在乳腺癌转移的生物学过程中存在一种可能新出现的分子途径。在此过程中，非Smad TGF-β诱导的转移通过一条核心途径“转移途径”连接癌症干细胞和转移小生境的形成。
