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Med Hypotheses. 2013 Sep;81(3):489-95. doi: 10.1016/j.mehy.2013.05.037. Epub 2013 Jul 12.
Cancer stem cells in a tumor mass form a very small subpopulation ranging from below 0.1% in a brain tumor but they have the crucial ability to become malignant. The goal of cancer therapy has been the total killing of tumor cells. However we should clarify that most of all tumor cells are differentiated cancer cells. Thus the elimination of 99.9% of tumor cells under histological criteria cannot ensure the cancer will be cured. Rather cancer cell biologists should turn their attention to reprogramming cancer stem cells to normal stem cells by which malignancy recuperates normal organogenesis from the aspect of the dichotomy of cancer stem cell. The cue points underlying the reverse cancer stem cell at blastogenesis in inflammation site is depending upon cell-to-cell recognition of the tumor-niche cells. Normalization of tumor-niche promises to lead cancer stem cell into normal stem cell owing to autonomous healing mechanisms that reside in the self-defense mechanisms in immunity and the cell competition mechanisms in the wound healing of the tissue cells. Among the cyto-skeletal proteins, vimentin becomes a target of self-restoration of cancer stem cell by means of immune surveillance. A human monoclonal antibody, CLN-IgG recognizes vimentin expressing on the cell surface of the malignant tumor. Since vimentin network resides in the cytoplasm connecting the plasma membrane with chromatin assembly in the nucleus, it is highly likely vimentin plays an important role in up-regulation and down-regulation through signal transduction between certain membrane receptors and gene expression with respect to the transformation of the cell. Aberrant arrangement of vimentin undergoes malignancy accompanied by epithelial-mesenchymal-transition relating to the aberrant apoptotic cellular behavior in the tumor-niche. Restraint of the aberrant expression of vimentin on the plasma membrane of the malignant cell evokes a pertinent signal transduction pathway for healing that is an indication there must be a reverse path that reprograms cancer stem cells to normal organogenesis.
肿瘤组织中的癌症干细胞形成一个非常小的亚群，在脑肿瘤中低于 0.1%，但它们具有恶性转化的关键能力。癌症治疗的目标一直是彻底杀死肿瘤细胞。然而，我们应该澄清的是，大多数肿瘤细胞都是分化的癌细胞。因此，根据组织学标准消除 99.9%的肿瘤细胞并不能确保癌症得到治愈。相反，癌症细胞生物学家应该将注意力转向通过重新编程癌症干细胞为正常干细胞来恢复恶性肿瘤的正常器官发生，这是从癌症干细胞二分法的角度来考虑的。炎症部位发生胚系肿瘤干细胞逆转的关键在于肿瘤-微环境细胞之间的细胞间识别。肿瘤-微环境的正常化有望使癌症干细胞向正常干细胞转化，这是由于免疫系统中的自主愈合机制和组织细胞创伤愈合中的细胞竞争机制。在细胞骨架蛋白中，波形蛋白成为免疫监视下癌症干细胞自我修复的靶标。一种人源单克隆抗体 CLN-IgG 识别恶性肿瘤细胞表面表达的波形蛋白。由于波形蛋白网络存在于细胞质中，将质膜与核内染色质组装连接起来，因此很可能波形蛋白在某些膜受体和基因表达之间的信号转导中通过细胞转化发挥重要作用。波形蛋白的异常排列伴随着上皮-间充质转化经历恶性转化，这与肿瘤微环境中异常的细胞凋亡行为有关。对恶性细胞质膜上异常表达的波形蛋白的抑制会引发相关的愈合信号转导途径，这表明一定存在一种反向途径，可以将癌症干细胞重新编程为正常器官发生。
