Platelet releasates promote the proliferation of hepatocellular carcinoma cells by suppressing the expression of KLF6

Abstract Platelets in the primary tumor microenvironment play crucial roles in the regulation of tumor progression, but the mechanisms underlying are poorly understood. Here, we report that platelet releasates exerted a proliferative effect on hepatocellular carcinoma (HCC) cells both in vitro and i...

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Autores principales:	Ao-Di He, Wen Xie, Wei Song, Yuan-Yuan Ma, Gang Liu, Ming-Lu Liang, Xing-Wen Da, Guang-Qiang Yao, Bi-xiang Zhang, Cun-Ji Gao, Ji-zhou Xiang, Zhang-Yin Ming
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/df8f2f0022fc4071bad4199551271286
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spelling	oai:doaj.org-article:df8f2f0022fc4071bad41995512712862021-12-02T16:08:19ZPlatelet releasates promote the proliferation of hepatocellular carcinoma cells by suppressing the expression of KLF610.1038/s41598-017-02801-12045-2322https://doaj.org/article/df8f2f0022fc4071bad41995512712862017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02801-1https://doaj.org/toc/2045-2322Abstract Platelets in the primary tumor microenvironment play crucial roles in the regulation of tumor progression, but the mechanisms underlying are poorly understood. Here, we report that platelet releasates exerted a proliferative effect on hepatocellular carcinoma (HCC) cells both in vitro and in vivo. This effect depended on a reduction of KLF6 expression in HCC cells. After incubation with either platelets or platelet granule contents, SMMC.7721 and HepG2 cells exhibited significant increases in proliferation and decreases in apoptosis. However, no effect was observed when incubating cancer cells with resuspended activated platelet pellet which exhausted of releasates. Platelet releasates also increased the population of HCC cells in the S and G2/M phases of the cell cycle and reduced the cell population in the G0/G1 phase. Moreover, knocking down KLF6 expression significantly diminished the platelet-mediated enhancement of HCC growth. In addition, blocking TGF-β signaling with the TGF-β receptor inhibitor SB431542 counteracted the effect of platelets on KLF6 expression and proliferation of HCC cells. Based on these findings, we conclude that platelet releasates, especially TGF-β, promote the proliferation of SMMC.7721 and HepG2 cells by decreasing expression of KLF6. This discovery identifies a potential new therapeutic target for the prevention and treatment of hepatocellular carcinoma.Ao-Di HeWen XieWei SongYuan-Yuan MaGang LiuMing-Lu LiangXing-Wen DaGuang-Qiang YaoBi-xiang ZhangCun-Ji GaoJi-zhou XiangZhang-Yin MingNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ao-Di He Wen Xie Wei Song Yuan-Yuan Ma Gang Liu Ming-Lu Liang Xing-Wen Da Guang-Qiang Yao Bi-xiang Zhang Cun-Ji Gao Ji-zhou Xiang Zhang-Yin Ming Platelet releasates promote the proliferation of hepatocellular carcinoma cells by suppressing the expression of KLF6
description	Abstract Platelets in the primary tumor microenvironment play crucial roles in the regulation of tumor progression, but the mechanisms underlying are poorly understood. Here, we report that platelet releasates exerted a proliferative effect on hepatocellular carcinoma (HCC) cells both in vitro and in vivo. This effect depended on a reduction of KLF6 expression in HCC cells. After incubation with either platelets or platelet granule contents, SMMC.7721 and HepG2 cells exhibited significant increases in proliferation and decreases in apoptosis. However, no effect was observed when incubating cancer cells with resuspended activated platelet pellet which exhausted of releasates. Platelet releasates also increased the population of HCC cells in the S and G2/M phases of the cell cycle and reduced the cell population in the G0/G1 phase. Moreover, knocking down KLF6 expression significantly diminished the platelet-mediated enhancement of HCC growth. In addition, blocking TGF-β signaling with the TGF-β receptor inhibitor SB431542 counteracted the effect of platelets on KLF6 expression and proliferation of HCC cells. Based on these findings, we conclude that platelet releasates, especially TGF-β, promote the proliferation of SMMC.7721 and HepG2 cells by decreasing expression of KLF6. This discovery identifies a potential new therapeutic target for the prevention and treatment of hepatocellular carcinoma.
format	article
author	Ao-Di He Wen Xie Wei Song Yuan-Yuan Ma Gang Liu Ming-Lu Liang Xing-Wen Da Guang-Qiang Yao Bi-xiang Zhang Cun-Ji Gao Ji-zhou Xiang Zhang-Yin Ming
author_facet	Ao-Di He Wen Xie Wei Song Yuan-Yuan Ma Gang Liu Ming-Lu Liang Xing-Wen Da Guang-Qiang Yao Bi-xiang Zhang Cun-Ji Gao Ji-zhou Xiang Zhang-Yin Ming
author_sort	Ao-Di He
title	Platelet releasates promote the proliferation of hepatocellular carcinoma cells by suppressing the expression of KLF6
title_short	Platelet releasates promote the proliferation of hepatocellular carcinoma cells by suppressing the expression of KLF6
title_full	Platelet releasates promote the proliferation of hepatocellular carcinoma cells by suppressing the expression of KLF6
title_fullStr	Platelet releasates promote the proliferation of hepatocellular carcinoma cells by suppressing the expression of KLF6
title_full_unstemmed	Platelet releasates promote the proliferation of hepatocellular carcinoma cells by suppressing the expression of KLF6
title_sort	platelet releasates promote the proliferation of hepatocellular carcinoma cells by suppressing the expression of klf6
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/df8f2f0022fc4071bad4199551271286
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Platelet releasates promote the proliferation of hepatocellular carcinoma cells by suppressing the expression of KLF6

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