Tumor cell-educated periprostatic adipose tissue acquires an aggressive cancer-promoting secretory profile.

Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology

PubMedID: 22415092

Ribeiro RJ, Monteiro CP, Cunha VF, Azevedo AS, Oliveira MJ, Monteiro R, Fraga AM, Príncipe P, Lobato C, Lobo F, Morais A, Silva V, Sanches-Magalhães J, Oliveira J, Guimarães JT, Lopes CM, Medeiros RM. Tumor cell-educated periprostatic adipose tissue acquires an aggressive cancer-promoting secretory profile. Cell Physiol Biochem. 2012;29(1-2):233-40.
BACKGROUND/AIMS
The microenvironment produces important factors that are crucial to prostate cancer (PCa) progression. However, the extent to which the cancer cells stimulate periprostatic adipose tissue (PPAT) to produce these proteins is largely unknown. Our purpose was to determine whether PCa cell-derived factors influence PPAT metabolic activity.

METHODS
Primary cultures of human PPAT samples from PCa patients (adipose tissue organotypic explants and primary stromal vascular fraction, SVF) were stimulated with conditioned medium (CM) collected from prostate carcinoma (PC3) cells. Cultures without CM were used as control. We used multiplex analysis and ELISA for protein quantification, qPCR to determine mitochondrial DNA (mtDNA) copy number and zymography for matrix metalloproteinase activity, in order to evaluate the response of adipose tissue explants and SVFs to PC3 CM.

RESULTS
Stimulation of PPAT explants with PCa PC3 CM induced adipokines associated with cancer progression (osteopontin, tumoral necrosis factor alpha and interleukin-6) and reduced the expression of the protective adipokine adiponectin. Notably, osteopontin protein expression was 13-fold upregulated. Matrix metalloproteinase 9 activity and mitochondrial DNA copy number were higher after stimulation with cancer CM. Stromovascular cells from PPAT in culture were not influenced by tumor-derived factors.

CONCLUSION
The modulation of adipokine expression by tumor CM indicates the pervasive extent to which tumor cells command PPAT to produce factors favorable to their aggressiveness.