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- W4386689621 abstract "Pancreatic 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." @default.
- W4386689621 created "2023-09-13" @default.
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- W4386689621 date "2023-09-12" @default.
- W4386689621 modified "2023-09-27" @default.
- W4386689621 title "The inhibition of pancreatic cancer progression by K-Ras-overexpressing mesenchymal stem cell-derived secretomes" @default.
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- W4386689621 doi "https://doi.org/10.1038/s41598-023-41835-6" @default.
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