Int J Med Sci 2020; 17(5):609-619. doi:10.7150/ijms.41354 This issue

Research Paper

Adipose Tissue-Derived Mesenchymal Stem Cells Suppress Growth of Huh7 Hepatocellular Carcinoma Cells via Interferon (IFN)-β-Mediated JAK/STAT1 Pathway in vitro

Chun Sung Byun1#, Soonjae Hwang2,6#, Sung-Hun Woo4, Moon Young Kim2,5, Jin Suk Lee2, Jong In Lee5, Jee Hyun Kong5, Keum Seok Bae3, Il Hwan Park1, Sung Hoon Kim3✉, Young Woo Eom2,6✉

1. Department of Cardiovascular and Thoracic Surgery, Yonsei University Wonju College of Medicine, Wonju, Gangwon-do 26426, Republic of Korea.
2. Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Gangwon-do 26426, Republic of Korea.
3. Department of General Surgery, Yonsei University Wonju College of Medicine, Wonju, Gangwon-do 26426, Republic of Korea.
4. Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju, Gangwon-do, 26493, Republic of Korea.
5. Department of Internal Medicine, Yonsei University Wonju College of Medicine, Gangwon-do 26426, Republic of Korea.
6. Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Gangwon-do 26426, Republic of Korea.
# These authors contributed equally to this work.

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Citation:
Byun CS, Hwang S, Woo SH, Kim MY, Lee JS, Lee JI, Kong JH, Bae KS, Park IH, Kim SH, Eom YW. Adipose Tissue-Derived Mesenchymal Stem Cells Suppress Growth of Huh7 Hepatocellular Carcinoma Cells via Interferon (IFN)-β-Mediated JAK/STAT1 Pathway in vitro. Int J Med Sci 2020; 17(5):609-619. doi:10.7150/ijms.41354. Available from https://www.medsci.org/v17p0609.htm

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Abstract

Interferon (IFN)-β and/or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) secreted by adipose tissue-derived mesenchymal stem cells (ASCs) have been proposed as key mechanistic factors in anti-cancer efficacy in lung cancer and breast cancer cells, where they act through paracrine signaling. We hypothesized that IFN-β and TRAIL produced by ASCs suppress proliferation of hepatocellular carcinoma cells (HCCs). The present study evaluated the anti-cancer effects of ASCs on HCCs in vitro. We found that indirect co-culture with ASCs diminished growth of Huh7 hepatocellular carcinoma cells with increased protein levels of p53/p21 and phosphorylated STAT1 (pSTAT1), without apoptosis. Treatment with ASC-conditioned medium (ASC-CM) also decreased growth of Huh7 cells through elevated p53/p21 and pSTAT1 signaling. ASC-CM-mediated inhibition of cell growth was neutralized in Huh7 cells treated with anti-IFN-β antibody compared to that in ASC-CM-treated Huh7 cells incubated with an anti-TRAIL antibody. Treatment with JAK1/JAK2 inhibitors recovered inhibition of growth in Huh7 cells incubated in ASC-CM or IFN-β via down-regulation of pSTAT1/p53/p21. However, treatment of IFN-β resulted in no alterations in resistance of Huh7 cells to TRAIL. Our findings suggest that ASCs decrease growth through activated STAT1-mediated p53/p21 by IFN-β, but not TRAIL, in Huh7 cells.