Adipsin-dependent secretion of hepatocyte growth factor regulates the adipocyte-cancer stem cell interaction

Masahiro Mizuno, Behnoush Khaledian, Masao Maeda, Takanori Hayashi, Seiya Mizuno, Eiji Munetsuna, Takashi Watanabe, Seishi Kono, Seiji Okada, Motoshi Suzuki, Shintaro Takao, Hironobu Minami, Naoya Asai, Fumihiro Sugiyama, Satoru Takahashi, Yohei Shimono

Research output: Contribution to journalArticlepeer-review

Abstract

Adipose tissue is a component of the tumor microenvironment and is involved in tumor progression. We have previously shown that adipokine adipsin (CFD) functions as an enhancer of tumor proliferation and cancer stem cell (CSC) properties in breast cancers. We established the Cfd-knockout (KO) mice and the mammary adipose tissue-derived stem cells (mADSCs) from them. Cfd-KO in mADSCs significantly reduced their ability to enhance tumorsphere formation of breast cancer patient-derived xenograft (PDX) cells, which was restored by the addition of Cfd in the culture medium. Hepatocyte growth factor (HGF) was expressed and secreted from mADSCs in a Cfd-dependent manner. HGF rescued the reduced ability of Cfd-KO mADSCs to promote tumorsphere formation in vitro and tumor formation in vivo by breast cancer PDX cells. These results suggest that HGF is a downstream effector of Cfd in mADSCs that enhances the CSC properties in breast cancers.

Original languageEnglish
Article number4238
JournalCancers
Volume13
Issue number16
DOIs
Publication statusPublished - 02-08-2021

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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