Systemic PPAR gamma Antagonism Reduces Metastatic Tumor Progression in Adipocyte-Rich Bone in Excess Weight Male Rodents

Gaculenko A, Gregoric G, Popp V, Seyler L, Ringer M, Kachler K, Wu Z, Kisel W, Hofbauer C, Hofbauer LC, Uder M, Schett G, Bäuerle T, Bozec A (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Journal of Bone and Mineral Research American Society for Bone and Mineral Research

DOI: 10.1002/jbmr.4422

Abstract

Primary tumors are widely associated with an excess in body fat. The role of adipose tissue on tumor cell homing to bone is yet poorly defined. In this study, we aimed to assess whether bone colonization by tumor cells is favored by an adipocyte-rich bone marrow. We delineated the accompanying alterations of the bone microenvironment and established a treatment approach that interferes with high fat diet (HFD)-induced bone metastasis formation. We were able to show that adipocytes affect skeletal tumor growth in a metastatic model of breast cancer in male rats and melanoma in male mice as well as in human breast cancer bone biopsies. Indeed, HFD-induced bone marrow adiposity was accompanied by accelerated tumor progression and increased osteolytic lesions. In human bone metastases, bone marrow adiposity correlated with tumor cell proliferation. By antagonization of the adipocyte differentiation and storage pathway linked to the peroxisome proliferator-activated receptor gamma (PPAR gamma) with bisphenol-A-diglycidylether (BADGE), we were able to decelerate tumor progression and subsequent osteolytic damage in the bones of two distinct metastatic animal models exposed to HFD. Overall these data show that adipose tissue is a critical factor in bone metastases and cancer-induced bone loss. 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Authors with CRIS profile

Anastasia Gaculenko Department of Medicine 3 – Rheumatology and Immunology Vanessa Popp Lehrstuhl für Mikroskopische Anatomie und Molekulare Zellbiologie Mark Ringer Department of Medicine 3 – Rheumatology and Immunology Katerina Kachler Department of Medicine 3 – Rheumatology and Immunology Zhengquan Wu Professur für Experimentelle Immuntherapie Michael Uder Lehrstuhl für Diagnostische Radiologie Georg Schett Lehrstuhl für Innere Medizin III Tobias Bäuerle Professur für Multimodale Bildgebung in der präklinischen Forschung Aline Bozec Professur für Experimentelle Immuntherapie

Involved external institutions

Technische Universität Dresden DE Germany (DE)

How to cite

APA:

Gaculenko, A., Gregoric, G., Popp, V., Seyler, L., Ringer, M., Kachler, K.,... Bozec, A. (2021). Systemic PPAR gamma Antagonism Reduces Metastatic Tumor Progression in Adipocyte-Rich Bone in Excess Weight Male Rodents. Journal of Bone and Mineral Research. https://doi.org/10.1002/jbmr.4422

MLA:

Gaculenko, Anastasia, et al. "Systemic PPAR gamma Antagonism Reduces Metastatic Tumor Progression in Adipocyte-Rich Bone in Excess Weight Male Rodents." Journal of Bone and Mineral Research (2021).

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