通过模拟胚胎微环境逆转肿瘤的研究进展

• 作 者: 申骏龙 雷光焰 吕卫东
• 机 构: 陕西省肿瘤医院胸外科,陕西中医学院附属医院,
• 出 处: 现代生物医学进展
• 发表日期: 2015年11期
• 关键词: 微环境 肿瘤干细胞 胚胎干细胞 组织工程 自我更新能力 细胞分化 分子机制研究 基质细胞 侵袭性肿瘤细胞 多向分化能力

肿瘤的发生和发展源于一小部分具有自我更新能力的肿瘤干细胞。胚胎干细胞也具有自我更新和多向分化的特性。胚胎干细胞特异的基质微环境能够提供干细胞正常生长的调控分子,在细胞不断更新的情况下,使增殖和分化达到平衡。受胚胎干细胞调节的基质或胚胎微环境作用于肿瘤细胞,可以使肿瘤细胞获得更多的分化表型,显著降低其恶性程度,抑制肿瘤细胞的侵袭行为。进一步的分子机制研究发现,在肿瘤细胞中高表达的Nodal蛋白会抑制肿瘤细胞分化,而胚胎干细胞分泌的糖基化Lefty蛋白可以负反馈调节Nodal蛋白的作用,从而降低肿瘤细胞的恶性程度。利用组织工程来模拟胚胎干细胞微环境,保留Lefty蛋白,从而逆转肿瘤的方法具有广阔的前景。

Tumor occurrence and development stems from a small part of self-renewing tumor stem cells. Embryonic stem cells also have the characteristics of self-renewal and multi-directional differentiation. Embryonic stem cell-specific stromal microenvironments provide regulators of normal stem cell growth that balance proliferation and differentiation as cells continue to renew. Embryonic stem cell-mediated matrix or embryonic microenvironment acting on tumor cells, tumor cells can make more differentiated phenotypes, significantly reducing the degree of malignancy, inhibiting tumor cell invasion behavior. Further molecular mechanism studies showed that Nodal protein highly expressed in tumor cells inhibited tumor cell differentiation, while glycosylated Lefty protein secreted by embryonic stem cells could negatively regulate the effect of Nodal protein and thus reduce the malignant degree of tumor cells. The use of tissue engineering to simulate the embryonic stem cell microenvironment and retain the Lefty protein, which reverse the tumor has broad prospects for the method.