Crosstalk Between Omental Adipose-Derived Stem Cells and Gastric Cancer Cells Regulates Cancer Stemness and Chemotherapy Resistance

网膜脂肪干细胞与胃癌细胞之间的串扰调节癌症干性和化疗耐药性

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作者:Jun Kinoshita, Kenta Doden, Yusuke Sakimura, Saki Hayashi, Hiroto Saito, Toshikatsu Tsuji, Daisuke Yamamoto, Hideki Moriyama, Toshinari Minamoto, Noriyuki Inaki

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.

Conclusion

This study improves our understanding of ASCs' role in PM treatment resistance and has demonstrated the potential for new treatment strategies targeting ASCs.

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.

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