2. Academic Validation
  3. The inhibition of pancreatic cancer progression by K-Ras-overexpressing mesenchymal stem cell-derived secretomes

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

  • Sci Rep. 2023 Sep 12;13(1):15036. doi: 10.1038/s41598-023-41835-6.
Qingji Huo # 1 2,  Kexin Li # 1 2,  Xun Sun 1 2,  Adam Zhuang 2,  Kazumasa Minami 3,  Keisuke Tamari 3,  Kazuhiko Ogawa 3,  Melissa L Fishel 4 5 6,  Bai-Yan Li 7,  Hiroki Yokota 8 9 10
Affiliations

Affiliations

  • 1 Department of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin, 150081, China.
  • 2 Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN, 46202, USA.
  • 3 Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
  • 4 Department of Pediatrics, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
  • 5 Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
  • 6 Indiana University Simon Comprehensive Cancer Center, Indianapolis, IN, 46202, USA.
  • 7 Department of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin, 150081, China. [email protected].
  • 8 Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN, 46202, USA. [email protected].
  • 9 Indiana University Simon Comprehensive Cancer Center, Indianapolis, IN, 46202, USA. [email protected].
  • 10 Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. [email protected].
  • # Contributed equally.
PMID: 37699930 DOI: 10.1038/s41598-023-41835-6
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.

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