Co-culture reduces cell proliferation in gastric cancer organoids, indicating mesothelial cells contribute to drug resistance mechanisms.
Abstract The prognosis of gastric cancer with peritoneal dissemination is poor because of its resistance to chemotherapy. To create an in vitro model of peritoneal metastases, cancer organoids were established from ascites fluid of patients with peritoneal metastases of gastric cancer. The histological characteristics of the tumors were preserved in the organoids. A co-culture system was established by overlaying human-derived mesothelial cells on gastric cancer organoids embedded in type I collagen, mimicking peritoneal dissemination foci. When co-cultured with mesothelial cells, the proliferation of ascites-derived gastric cancer organoids and other primary gastric cancer organoids was suppressed. Soluble factors derived from mesothelial cells were involved in suppressing cell proliferation. Organoids in co-culture showed reduced sensitivity to paclitaxel. This co-culture model may provide a useful platform for studying drug resistance mechanisms in the microenvironment of gastric cancer peritoneal metastases.
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Inoue et al. (2025) studied this question.
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