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Submitted on February 1, 2005
Proteomics in Cancer, Institute of Cancer Biology, Danish Cancer Society, Copenhagen 2100
Corresponding Author: jec{at}cancer.dk
It has become clear that growth and progression of breast tumor cells not only depends on their malignant potential, but also on factors present in the tumour microenvironment. Of the cell types that constitute the mammary stroma, the adipocytes are perhaps the less well studied despite the fact that they represent one of the most prominent cell types surrounding the breast tumor cells. There is compelling evidence demonstrating a role for the mammary fat pad in mammary gland development, and some studies have revealed the ability of fat tissue to augment the growth and metastasising ability of mammary carcinoma cells. Very little is known, however, about which factors adipocytes produce that may orchestrate these actions, and how this may come about. In an effort to shed some light on these questions, we present here a detailed proteomic analysis - using 2D gel-based technology, mass spectrometry, immunoblotting and antibody arrays – of adipose cells and interstitial fluid of fresh fat tissue samples collected distant to the tumors of high-risk breast cancer patients that underwent mastectomy and that were not treated prior to surgery. A total of 359 unique proteins were identified - including numerous signaling molecules, hormones, cytokines as well as growth factors - involved in a variety of biological processes such as signal transduction and cell communication, energy metabolism, protein metabolism, cell growth and/or maintenance, immune response, transport, nucleic acid metabolism, and apoptosis. Apart from providing a comprehensive overview of the mammary fat proteome and its interstitial fluid, the results offer some insight as to the role of adipocytes in the breast tumor microenvironment, and provide a first glance of their molecular cellular circuitry. In addition, the results open new possibilities to the study of obesity, which has a strong association with type 2-diabetes, hypertension and coronary heart disease.
Revised on February 2, 2005
Accepted on February 2, 2005
Identification of extracellular and intracellular signaling components of the mammary adipose tissue and its interstitial fluid in high-risk breast cancer patients: Towards dissecting the molecular circuitry of epithelial-adipocyte stromal cell interactions
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