Bone marrow adipocytes promote tumor growth in bone via FABP4-dependent mechanisms
PDF | HTML | Supplementary Files | How to cite
Metrics: PDF 3093 views | HTML 4412 views | ?
Mackenzie K. Herroon1, Erandi Rajagurubandara1, Aimalie L. Hardaway1,3, Katelyn Powell1,2,3, Audrey Turchick4, Daniel Feldmann1,3, and Izabela Podgorski1,3
1 Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI
2 Pathology, Wayne State University School of Medicine, Detroit, MI
3 Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI
4 Therapeutic Radiology, Yale School of Medicine
Izabela Podgorski, email:
Keywords: bone marrow adipocytes, bone metastasis, prostate cancer, breast cancer, interleukin 1ß, heme oxygenase 1
Received: October 8, 2013 Accepted: October 27, 2013 Published: October 29, 2013
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.