整合素αvβ6 在结肠癌干细胞向高侵袭性结肠癌细胞分化中的作用研究

Adhesion molecule plays an important role in the regulation of biological characteristics of tumor stem cells. Our comprehensive research during the last 2 decades has confirmed that integrin αvβ6 is a critical factor promoting metastasis in colon cancer. Recently, we found that the capability of apoptosis resistance, proliferation, invasion and tumorigenic ability of αvβ6 positive colon cancer cells is correlative with drug resistance, proliferation, and higher tumorigenic characteristic of tumor stem cells. On the leading edge in tumor invasion αvβ6 and colon cancer stem cell marker expression are co-expression and co-localization. Most importantly, αvβ6 induced Epithelial-mesenchymal transition through activation of TGF-β1 and enhanced invasion and metastasis ability of tumor cells. This research is deepening and continued of our previous work. Based on the identification and isolation of cancer stem cells from a variety of colon cancer cell lines, we will explicate the role of αvβ6 played on the drug resistance, proliferation, higher tumorigenic characteristic of tumor stem cells from multiple levels including clinical specimens, animal models and cell experiments. We will reveal the mechanism and role of αvβ6 in the differentiation of stem cell into high invasion tumor cells. This research will answer whether αvβ6 can be a potential new surface marker for those colorectal cancer stem cell with high invasion ability. Our research will provide a potential treatment target for the therapy in colon cancer.

黏附分子在调控肿瘤干细胞生物学特性方面发挥重要作用，我们对整合素近20年研究证实αvβ6是促进结肠癌恶性进展的关键黏附分子。我们近期发现，表达αvβ6的结肠癌细胞表现出的抵御凋亡、增殖侵袭和成瘤能力与肿瘤干细胞的强耐药性、无限增殖、高致瘤性等特性相一致，且αvβ6在肿瘤侵袭边缘与结肠癌干细胞标记物共表达、共定位。尤为重要的是，αvβ6通过激活TGF-β1诱导上皮间质转化，增强肿瘤细胞的侵袭转移能力。本研究是前期工作的深化和延续，在对多种结肠癌细胞系进行干细胞分离鉴定的基础上，采用细胞、动物成瘤及转移瘤模型等多层次实验，明确αvβ6对结肠癌干细胞侵袭转移、化疗耐药的影响；揭示αvβ6在结肠癌干细胞向高侵袭性结肠癌细胞分化中的作用及机制；探讨αvβ6能否作为具有高侵袭潜能结肠癌干细胞的新型表面标记，为靶向治疗肿瘤干细胞，从源头上解决恶性肿瘤耐药、易转移和复发提供新的理论依据。

αvβ6是促进结肠癌恶性进展的关键黏附分子。我们发现，表达αvβ6的结肠癌细胞表现出的抵御凋亡、增殖侵袭和成瘤能力与肿瘤干细胞的强耐药性、无限增殖、高致瘤性等特性相一致，且αvβ6在肿瘤侵袭边缘与结肠癌干细胞标记物共表达、共定位。尤为重要的是，αvβ6通过激活TGF-β1诱导上皮间质转化，增强肿瘤细胞的侵袭转移能力。本课题组在前期工作基础上，对多种结肠癌细胞系进行干细胞分离鉴定，采用细胞，组织等多层次实验，明确了αvβ6对结肠癌干细胞侵袭转移、化疗耐药的影响；揭示了αvβ6在结肠癌干细胞向高侵袭性结肠癌细胞分化中的作用及机制，本研究最终结果初步认为αvβ6可作为具有高侵袭潜能结肠癌干细胞的新型表面标记，将来为靶向治疗肿瘤干细胞，从源头上解决恶性肿瘤耐药、易转移和复发提供初步的理论依据。