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 Byun; Soonjae Hwang; Sung Hun Woo; Moon Young Kim; Jin Suk Lee; Jong In Lee; Jee Hyun Kong; Keum Seok Bae; Il Hwan Park; Sung Hoon Kim; Young Woo Eom

doi:10.7150/ijms.41354

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 Byun, Soonjae Hwang, Sung Hun Woo, Moon Young Kim, Jin Suk Lee, Jong In Lee, Jee Hyun Kong, Keum Seok Bae, Il Hwan Park, Sung Hoon Kim, Young Woo Eom

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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.

Original language	English
Pages (from-to)	609-619
Number of pages	11
Journal	International Journal of Medical Sciences
Volume	17
Issue number	5
DOIs	https://doi.org/10.7150/ijms.41354
Publication status	Published - 2020

Bibliographical note

Funding Information:
This work was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI17C1365) and a Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Korean government, the Ministry of Education (NRF-2017R1D1A1A02019 212). In addition, the Yonsei University Wonju Campus Future-Leading Research Initiative of 2017 supported this work (2017-52-0079). This work was supported, in part, by the Yonsei University Research Fund of 2019.

Publisher Copyright:
© The author(s).

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10.7150/ijms.41354

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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

@article{dba34a9bc0e448faaadc69029b30adf9,

title = "Adipose tissue-derived mesenchymal stem cells suppress growth of Huh7 hepatocellular carcinoma cells via interferon (IFN)-β-mediated JAK/STAT1 pathway in vitro",

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.",

author = "Byun, {Chun Sung} and Soonjae Hwang and Woo, {Sung Hun} and Kim, {Moon Young} and Lee, {Jin Suk} and Lee, {Jong In} and Kong, {Jee Hyun} and Bae, {Keum Seok} and Park, {Il Hwan} and Kim, {Sung Hoon} and Eom, {Young Woo}",

note = "Funding Information: This work was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI17C1365) and a Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Korean government, the Ministry of Education (NRF-2017R1D1A1A02019 212). In addition, the Yonsei University Wonju Campus Future-Leading Research Initiative of 2017 supported this work (2017-52-0079). This work was supported, in part, by the Yonsei University Research Fund of 2019. Publisher Copyright: {\textcopyright} The author(s).",

year = "2020",

doi = "10.7150/ijms.41354",

language = "English",

volume = "17",

pages = "609--619",

journal = "International Journal of Medical Sciences",

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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', International Journal of Medical Sciences, vol. 17, no. 5, pp. 609-619. https://doi.org/10.7150/ijms.41354

TY - JOUR

T1 - Adipose tissue-derived mesenchymal stem cells suppress growth of Huh7 hepatocellular carcinoma cells via interferon (IFN)-β-mediated JAK/STAT1 pathway in vitro

AU - Byun, Chun Sung

AU - Hwang, Soonjae

AU - Woo, Sung Hun

AU - Kim, Moon Young

AU - Lee, Jin Suk

AU - Lee, Jong In

AU - Kong, Jee Hyun

AU - Bae, Keum Seok

AU - Park, Il Hwan

AU - Kim, Sung Hoon

AU - Eom, Young Woo

N1 - Funding Information: This work was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI17C1365) and a Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Korean government, the Ministry of Education (NRF-2017R1D1A1A02019 212). In addition, the Yonsei University Wonju Campus Future-Leading Research Initiative of 2017 supported this work (2017-52-0079). This work was supported, in part, by the Yonsei University Research Fund of 2019. Publisher Copyright: © The author(s).

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

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JO - International Journal of Medical Sciences

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Adipose tissue-derived mesenchymal stem cells suppress growth of Huh7 hepatocellular carcinoma cells via interferon (IFN)-β-mediated JAK/STAT1 pathway in vitro

Abstract

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