【文献解读】从人类结直肠癌分离的癌相关成纤维细胞作为促进转移的主要基质细胞成分的分子表征

【文献解读】从人类结直肠癌分离的癌相关成纤维细胞作为促进转移的主要基质细胞成分的分子表征
2017/7/13 创新医学网

     文章来源：欧尔意 OAE 微信号

     作者 :sofina

     原文出处

     Potdar PD, Chaudhary S. Molecular characterization of cancer-associated fibroblasts isolated from human colorectal cancer as a major stromal cell component promoting metastasis. J Unexplored Med Data 2017;2:1-8.

     DOI:10.20517/2572-8180.2016.10.

     摘要

     目的：结直肠癌仍然是一种预后不良，总体5年生存率有限的疾病，这突出了临床上对新型治疗策略的需求。基质癌相关成纤维细胞强烈地决定了结直肠癌的转移潜能，因此需要对临床结果进行调查。方法：作者建立了来自转移性结直肠癌患者的癌相关成纤维细胞的原代培养物，并使用相差显微镜和组织学染色，然后使用光学显微镜进行细胞鉴定。进一步探讨分离的癌相关成纤维细胞用于促进转移过程的基因的分子表征。结果：基质癌相关成纤维细胞在体外保持其成纤维细胞表型，表现出高增殖潜力。为了探索基因表达谱，从癌相关成纤维细胞的原代培养物中分离出总RNA，进行定性RT-PCR。培养的癌相关成纤维细胞显示与癌症干细胞，上皮细胞间质转化诱导和炎性细胞因子/趋化因子有关的转移相关的基因特征。这些基因在化疗耐药中起关键作用，也与结直肠癌预后不良有关。结论：该研究进一步描述了癌症相关成纤维细胞作为肿瘤微环境中“损坏”基质细胞的一部分在建立和编排结直肠癌转移命运中的作用。基因表达谱清楚地表明，癌症相关的成纤维细胞是改善结直肠癌治疗的潜在靶标。

     关键词：癌相关成纤维细胞，上皮细胞向间质细胞转化，转移，结直肠癌，基质细胞。

     Aim: Colorectal cancer (CRC) remains a disease with poor prognosis and limited overall 5-year survival rate, which highlights a clear clinical need for novel treatment strategies. The stromal cancer-associated fibroblasts (CAFs) strongly dictate the metastatic potential of CRC and hence warrant investigation for clinical outcome. Methods: The authors established primary cultures of CAFs from metastatic CRC patients and performed cellular characterization using phase contrast microscopy and histological staining followed by light microscopy. The isolated CAFs were further explored for the molecular characterization of genes which promote the process of metastasis. Results:The stromal CAFs maintain their fibroblastic phenotype in vitro and manifested high proliferation potential. To explore the gene expression profile, total RNA was isolated from the primary culture of CAFs and qualitative RT-PCR was performed. The cultured CAFs exhibited gene signatures associated with cancer stemness, epithelial to mesenchymal transition induction and inflammatory cytokines/chemokines favoring metastasis. These genes play a pivotal role in chemotherapy resistance and are also associated with poor prognosis in CRC. Conclusion: This study further delineates the role of CAFs as a part of the “corrupted” stromal cells within the tumor microenvironment in establishing and orchestrating the metastatic fate of CRC. The gene expression profile clearly indicates that CAFs represent a potential target for improved therapy of CRC.

     Keywords:Cancer-associated fibroblasts, epithelial to mesenchymal transition, metastasis, colorectal cancer, stromal cells.

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