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Bone marrow adipocytes promote tumor growth in bone via FABP4-dependent mechanisms

Overview of attention for article published in Oncotarget, October 2013
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Title
Bone marrow adipocytes promote tumor growth in bone via FABP4-dependent mechanisms
Published in
Oncotarget, October 2013
DOI 10.18632/oncotarget.1482
Pubmed ID
Authors

Mackenzie K. Herroon, Erandi Rajagurubandara, Aimalie L. Hardaway, Katelyn Powell, Audrey Turchick, Daniel Feldmann, Izabela Podgorski

Abstract

Incidence of skeletal metastases and death from prostate cancer greatly increases with age and obesity, conditions which increase marrow adiposity. Bone marrow adipocytes are metabolically active components of bone metastatic niche that modulate the function of neighboring cells; yet the mechanisms of their involvement in tumor behavior in bone have not been explored. In this study, using experimental models of intraosseous tumor growth and diet-induced obesity, we demonstrate the promoting effects of marrow fat on growth and progression of skeletal prostate tumors. We reveal that exposure to lipids supplied by marrow adipocytes induces expression of lipid chaperone FABP4, pro-inflammatory interleukin IL-1β, and oxidative stress protein HMOX-1 in metastatic tumor cells and stimulates their growth and invasiveness. We show that FABP4 is highly overexpressed in prostate skeletal tumors from obese mice and in bone metastasis samples from prostate cancer patients. In addition, we provide results suggestive of bi-directional interaction between FABP4 and PPARγ pathways that may be driving aggressive tumor cell behavior in bone. Together, our data provide evidence for functional relationship between bone marrow adiposity and metastatic prostate cancers and unravel the FABP4/IL-1β axis as a potential therapeutic target for this presently incurable disease.

Mendeley readers

The data shown below were compiled from readership statistics for 102 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 <1%
United States 1 <1%
Italy 1 <1%
Unknown 99 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 34 33%
Researcher 22 22%
Student > Bachelor 9 9%
Student > Doctoral Student 5 5%
Student > Master 5 5%
Other 10 10%
Unknown 17 17%
Readers by discipline Count As %
Agricultural and Biological Sciences 28 27%
Biochemistry, Genetics and Molecular Biology 25 25%
Medicine and Dentistry 16 16%
Pharmacology, Toxicology and Pharmaceutical Science 2 2%
Neuroscience 1 <1%
Other 8 8%
Unknown 22 22%