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

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.

✉ Corresponding authors: Young Woo Eom, Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Gangwon-do 26426, Republic of Korea. Tel: +82-33-741-0260. E-mail: yweomac.kr. Sung Hoon Kim, Department of More

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. 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.

Citation styles

APA
Byun, C.S., Hwang, S., Woo, S.H., Kim, M.Y., Lee, J.S., Lee, J.I., Kong, J.H., Bae, K.S., Park, I.H., Kim, S.H., Eom, Y.W. (2020). Adipose Tissue-Derived Mesenchymal Stem Cells Suppress Growth of Huh7 Hepatocellular Carcinoma Cells via Interferon (IFN)-β-Mediated JAK/STAT1 Pathway in vitro. International Journal of Medical Sciences, 17(5), 609-619. https://doi.org/10.7150/ijms.41354.

ACS
Byun, C.S.; Hwang, S.; Woo, S.H.; Kim, M.Y.; Lee, J.S.; Lee, J.I.; Kong, J.H.; Bae, K.S.; Park, I.H.; Kim, S.H.; Eom, Y.W. 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.

NLM
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. https://www.medsci.org/v17p0609.htm

CSE
Byun CS, Hwang S, Woo SH, Kim MY, Lee JS, Lee JI, Kong JH, Bae KS, Park IH, Kim SH, Eom YW. 2020. 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. 17(5):609-619.

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