Kinoshita Jun, Doden Kenta, Sakimura Yusuke, Hayashi Saki, Saito Hiroto, Tsuji Toshikatsu, Yamamoto Daisuke, Moriyama Hideki, Minamoto Toshinari, Inaki Noriyuki
Department of Gastrointestinal Surgery, Kanazawa University, Kanazawa 920-8641, Japan.
Japan Community Health Care Organization Kanazawa Hospital, Kanazawa 920-8610, Japan.
Cancers (Basel). 2024 Dec 23;16(24):4275. doi: 10.3390/cancers16244275.
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. : ASCs were isolated from the human omentum and their cellular characteristics were analyzed during co-culturing with GC cells. 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. This study improves our understanding of ASCs' role in PM treatment resistance and has demonstrated the potential for new treatment strategies targeting ASCs.
腹膜转移（PM）仍是胃癌（GC）患者面临的一项重大挑战，且优先发生于富含脂肪的器官，如大网膜。脂肪来源干细胞（ASC）可能影响癌症行为。本研究旨在调查从大网膜分离出的ASC是否可作为癌相关成纤维细胞（CAF）的祖细胞，并分析它们对癌症干细胞（CSC）微环境及GC细胞治疗抗性的影响。从人网膜中分离出ASC，并在与GC细胞共培养期间分析其细胞特征。在小鼠异种移植模型中，ASC表达CAF标志物并促进癌基质中的结缔组织增生。当与GC细胞共培养时，ASC提高了MKN45和MKN74细胞的成球效率。ASC增加了IL-6分泌并增强了GC细胞中Nanog和CD44v6的表达；然而，这些变化可通过抑制IL-6来抑制。与MKN45细胞和ASC共同接种的异种移植小鼠模型显示CD44v6和Nanog表达增强，且5-氟尿嘧啶治疗诱导的细胞凋亡明显减少。本研究增进了我们对ASC在PM治疗抗性中作用的理解，并证明了针对ASC的新治疗策略的潜力。
