Background:Peritoneal metastasis (PM) remains a major challenge in patients with gastric cancer (GC) and occurs preferentially in adipose-rich organs, such as the omentum. Adipose-derived stem cells (ASCs) may influence cancer behavior. This study aimed to investigate whether ASCs isolated from the omentum can act as progenitors of cancer-associated fibroblasts (CAFs) and analyze their effects on the cancer stem cell (CSC) niche and the treatment resistance of GC cells.Methods: ASCs were isolated from the human omentum and their cellular characteristics were analyzed during co-culturing with GC cells.Results:ASCs express CAF markers and promote desmoplasia in cancer stroma in a mouse xenograft model. When co-cultured with GC cells, ASCs enhanced the sphere-forming efficiency of MKN45 and MKN74 cells. ASCs increased IL-6 secretion and enhanced the expression of Nanog and CD44v6 in GC cells; however, these changes were suppressed by the inhibition of IL-6. Xenograft mouse models co-inoculated with MKN45 cells and ASCs showed enhanced CD44v6 and Nanog expression and markedly reduced apoptosis induced by 5-FU treatment.Conclusion:This study improves our understanding of ASCs’ role in PM treatment resistance and has demonstrated the potential for new treatment strategies targeting ASCs.
背景：腹膜转移（PM）在胃癌（GC）患者中仍是一个主要挑战，且多发生于富含脂肪的器官，如大网膜。脂肪源性干细胞（ASCs）可能影响癌症行为。本研究旨在探讨从大网膜分离的ASCs是否能作为癌症相关成纤维细胞（CAFs）的前体细胞，并分析其对癌症干细胞（CSC）生态位及胃癌细胞治疗抵抗的影响。 方法：从人源大网膜中分离ASCs，并在与胃癌细胞共培养过程中分析其细胞特性。 结果：ASCs表达CAF标志物，并在小鼠异种移植模型中促进癌间质纤维增生。与胃癌细胞共培养时，ASCs增强了MKN45和MKN74细胞的成球效率。ASCs增加了IL-6分泌并促进胃癌细胞中Nanog和CD44v6的表达，但这些变化可通过抑制IL-6被阻断。共接种MKN45细胞与ASCs的异种移植小鼠模型显示CD44v6和Nanog表达增强，且5-FU治疗诱导的细胞凋亡显著减少。 结论：本研究增进了对ASCs在腹膜转移治疗抵抗中作用的理解，并展示了针对ASCs开发新治疗策略的潜力。
肿瘤(癌症)患者之家