Huo, QingjiLi, KexinSun, XunZhuang, AdamMinami, KazumasaTamari, KeisukeOgawa, KazuhikoFishel, Melissa L.Li, Bai‑YanYokota, Hiroki2024-03-082024-03-082023-09-12Huo Q, Li K, Sun X, et al. The inhibition of pancreatic cancer progression by K-Ras-overexpressing mesenchymal stem cell-derived secretomes. Sci Rep. 2023;13(1):15036. Published 2023 Sep 12. doi:10.1038/s41598-023-41835-6https://hdl.handle.net/1805/39117Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor survival. To explore an uncharted function of K-Ras proto-oncogene, K-Ras was activated in mesenchymal stem cells (MSCs) and the effects of MSC conditioned medium (CM) on PDAC were examined. Overexpression of K-Ras elevated PI3K signaling in MSCs, and K-Ras/PI3K-activated MSC-derived CM reduced the proliferation and migration of tumor cells, as well as the growth of ex vivo freshly isolated human PDAC cultures. CM's anti-tumor capability was additive with Gemcitabine, a commonly used chemotherapeutic drug in the treatment of PDAC. The systemic administration of CM in a mouse model suppressed the colonization of PDAC in the lung. MSC CM was enriched with Moesin (MSN), which acted as an extracellular tumor-suppressing protein by interacting with CD44. Tumor-suppressive CM was also generated by PKA-activated peripheral blood mononuclear cells. Collectively, this study demonstrated that MSC CM can be engineered to act as a tumor-suppressive agent by activating K-Ras and PI3K, and the MSN-CD44 regulatory axis is in part responsible for this potential unconventional option in the treatment of PDAC.en-USAttribution 4.0 InternationalDiseasesOncologyNeoplastic processesSecretomeArticle