Adipsin-Dependent Secretion of Hepatocyte Growth Factor Regulates the Adipocyte-Cancer Stem Cell Interaction

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

doi:10.3390/cancers13164238

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Adipsin-Dependent Secretion of Hepatocyte Growth Factor Regulates the Adipocyte-Cancer Stem Cell Interaction

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Department of Biochemistry, Fujita Health University School of Medicine, Toyoake 4701192, Japan

Department of Pathology, Fujita Health University School of Medicine, Toyoake 4701192, Japan

Laboratory Animal Resource Center, Transborder Medical Research Center, Faculty of Medicine, University of Tsukuba, Tsukuba 3058575, Japan

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Division of Breast and Endocrine Surgery, Kobe University Graduate School of Medicine, Kobe 6500017, Japan

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Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 8600811, Japan

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Department of Molecular Oncology, Fujita Health University School of Medicine, Toyoake 4701192, Japan

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Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe 6500017, Japan

Author to whom correspondence should be addressed.

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Equally contributed to this work.

Academic Editors: Eldad Zacksenhaus and Sean Egan

Cancers 2021, 13(16), 4238; https://doi.org/10.3390/cancers13164238

Received: 15 July 2021 / Revised: 18 August 2021 / Accepted: 19 August 2021 / Published: 23 August 2021

(This article belongs to the Special Issue From Progression to Metastasis of Solid Cancer)

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Obesity, which is characterized by the excess of adipose tissue, is associated with an increased risk of multiple cancers. We have previously reported that adipsin, a secreted factor from adipocytes, enhances cancer cell proliferation and stem cell properties. In this study, we found that adipsin affects adipocytes themselves and enhanced their secretion of hepatocyte growth factor (HGF). We found that HGF enhanced the adipocyte-cancer cell interactions as a downstream effector of adipsin. Understanding the adipocyte-cancer cell interaction will provide a novel strategy to treat cancers whose initiation, invasion, and metastatic progression are associated with adipose tissues.

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. View Full-Text

Keywords: adipocyte; cancer stem cells; adipsin; hepatocyte growth factor; breast cancer

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MDPI and ACS Style

Mizuno, M.; Khaledian, B.; Maeda, M.; Hayashi, T.; Mizuno, S.; Munetsuna, E.; Watanabe, T.; Kono, S.; Okada, S.; Suzuki, M.; Takao, S.; Minami, H.; Asai, N.; Sugiyama, F.; Takahashi, S.; Shimono, Y. Adipsin-Dependent Secretion of Hepatocyte Growth Factor Regulates the Adipocyte-Cancer Stem Cell Interaction. Cancers 2021, 13, 4238. https://doi.org/10.3390/cancers13164238

AMA Style

Mizuno M, Khaledian B, Maeda M, Hayashi T, Mizuno S, Munetsuna E, Watanabe T, Kono S, Okada S, Suzuki M, Takao S, Minami H, Asai N, Sugiyama F, Takahashi S, Shimono Y. Adipsin-Dependent Secretion of Hepatocyte Growth Factor Regulates the Adipocyte-Cancer Stem Cell Interaction. Cancers. 2021; 13(16):4238. https://doi.org/10.3390/cancers13164238

Chicago/Turabian Style

Mizuno, Masahiro, 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, and Yohei Shimono. 2021. "Adipsin-Dependent Secretion of Hepatocyte Growth Factor Regulates the Adipocyte-Cancer Stem Cell Interaction" Cancers 13, no. 16: 4238. https://doi.org/10.3390/cancers13164238

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Adipsin-Dependent Secretion of Hepatocyte Growth Factor Regulates the Adipocyte-Cancer Stem Cell Interaction

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