The inhibition of pancreatic cancer progression by K-Ras-overexpressing mesenchymal stem cell-derived secretomes

作者：Huo, Qingji; Li, Kexin; Sun, Xun; Zhuang, Adam; Minami, Kazumasa; Tamari, Keisuke; Ogawa, Kazuhiko; Fishel, Melissa L.; Li, Bai-Yan^*; Yokota, Hiroki^*

来源：Scientific Reports, 2023, 13(1): 15036.

DOI：10.1038/s41598-023-41835-6

• GEMCITABINE
• CD44
• EXPRESSION
• PATHWAYS
• SURVIVAL
• THERAPY
• BONE

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.

• 单位
  哈尔滨医科大学