Milk fat globule-EGF factor 8 contributes to progression of hepatocellular carcinoma

Duck Sung Ko, Su Hyun Kim, Ji Young Park, Gyunggyu Lee, Hyo Jin Kim, Gyeongmin Kim, Kyun You Chi, Ilsoo Kim, Jinseok Lee, Kyu Yeoun Won, Jiyou Han, Jeongsang Son, Dong Hun Woo, Choongseong Han, Jong Hoon Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Milk fat globule-EGF factor 8 (MFG-E8) is an anti-inflammatory glycoprotein that mediates a wide spectrum of pathophysiological processes. MFG-E8 has been studied as a key regulator of cancer cell invasion, migration, and proliferation in different tissues and organs. However, potential roles of MFG-E8 in the growth and progression of liver cancer have not been investigated to date. Here, we analyzed 33 human hepatocellular carcinoma (HCC) samples and found that levels of MFG-E8 expression were significantly higher in HCC cells than in normal liver tissues. In addition, our in vitro gain-of-function study in three different HCC cell lines revealed that overexpression of MFG-E8 promoted the proliferation and migration of HCC cells, as determined by RT-qPCR, MTT assays, and wound healing analyses. Conversely, an MFG-E8 loss-of function study showed that proliferation capacity was significantly reduced by MFG-E8 knockdown in HCC cells. Additionally, MFG-E8 activity-neutralizing antibodies profoundly inhibited both migration and proliferation of HCC cells, attenuating their tumorigenic properties. These reductions in migration and proliferation were rescued by treatment of HCC cells with recombinant MFG-E8 protein. Furthermore, an in vivo HCC xenograft study showed that the number of proliferating HCC cells and tumor volume/weight were all significantly increased by MFG-E8 overexpression, compared to control mice. These results clearly show that MFG-E8 plays an important role in HCC progression and may provide a basis for future mechanistic studies and new strategies for the treatment of liver cancer.

Original languageEnglish
Article number403
JournalCancers
Volume12
Issue number2
DOIs
Publication statusPublished - 2020 Feb

Keywords

  • Hepatocellular carcinoma
  • Migration
  • Milk fat globule-EGF factor 8
  • Proliferation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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