Differential modulation of cellular phenotype and drug sensitivity by extracellular matrix proteins in primary and metastatic pancreatic cancer cells.
Differential modulation of cellular phenotype and drug sensitivity by extracellular matrix proteins in primary and metastatic pancreatic cancer cells.
复制标题
原发性和转移性胰腺癌细胞中细胞外基质蛋白对细胞表型和药物敏感性的差异调节。
DOI：
10.1091/mbc.e23-02-0075
复制
发表时间：
2023
影响因子：
3.3
通讯作者：
Irianto,Jerome
中科院分区：
文献类型：
--
作者：
Usman,OlalekanH;Kumar,Sampath;Walker3rd,ReddickR;Xie,Gengqiang;Sumajit,HyejeC;Jalil,AbdelAzizR;Ramakrishnan,Subramanian;Dooling,LawrenceJ;Wang,YueJulia;Irianto,Jerome
据报道，胰腺导管腺癌 (PDAC) 是美国癌症相关死亡的第三大原因。 PDAC 以其高比例的基质而闻名，占肿瘤质量的 90%。基质由细胞外基质 (ECM) 和非恶性细胞组成，例如炎症细胞、癌症相关成纤维细胞、淋巴管和血管。在这里，我们通过在涂有不同 ECM 蛋白的表面上培养细胞来解耦 ECM 对 PDAC 细胞系的影响。我们的数据表明，原发性肿瘤来源的细胞系根据培养它们的 ECM 蛋白而具有不同的形态，而转移性病变来源的 PDAC 系的形态不会因不同的 ECM 蛋白而改变。类似地，ECM 蛋白调节原发性肿瘤 PDAC 细胞系的增殖率和吉西他滨敏感性，但不调节转移性 PDAC 细胞系。最后，对在不同 ECM 蛋白上培养的原发性肿瘤 PDAC 细胞的转录组学分析揭示了各种途径的调节，例如细胞周期、细胞粘附分子和粘着斑，包括对 ECM 识别至关重要的几个整合素基因的调节。
Pancreatic ductal adenocarcinoma (PDAC) is reported to be the third highest cause of cancer-related deaths in the United States. PDAC is known for its high proportion of stroma, which accounts for 90% of the tumor mass. The stroma is made up of extracellular matrix (ECM) and nonmalignant cells such as inflammatory cells, cancer-associated fibroblasts, and lymphatic and blood vessels. Here, we decoupled the effects of the ECM on PDAC cell lines by culturing cells on surfaces coated with different ECM proteins. Our data show that the primary tumor-derived cell lines have different morphology depending on the ECM proteins on which they are cultured, while metastatic lesion-derived PDAC lines’ morphology does not change with respect to the different ECM proteins. Similarly, ECM proteins modulate the proliferation rate and the gemcitabine sensitivity of the primary tumor PDAC cell lines, but not the metastatic PDAC lines. Lastly, transcriptomics analysis of the primary tumor PDAC cells cultured on different ECM proteins reveals the regulation of various pathways, such as cell cycle, cell-adhesion molecules, and focal adhesion, including the regulation of several integrin genes that are essential for ECM recognition.