Periprostatic Adipose Tissue as a Modulator of Prostate Cancer Aggressiveness

David S. Finley, Valerie S. Calvert, Junichi Inokuchi, Alice Lau, Navneet Narula, Emanuel F. Petricoin, Frank Zaldivar, Rosanne Santos, Darren R. Tyson, David K. Ornstein

Research output: Contribution to journalArticle

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Abstract

Purpose: Adipose tissue has been suggested to contribute to the pathogenesis of various disease states, including prostate cancer. We investigated the association of cytokines and growth factors secreted by periprostatic adipose tissue with pathological features of aggressive prostate cancer. Materials and Methods: Periprostatic adipose tissue was harvested from patients undergoing radical prostatectomy and cultured for 24 hours to generate conditioned medium or snap frozen immediately for functional signaling profiling. Multiplex analysis of the periprostatic adipose tissue conditioned medium was used to detect cytokine levels and compared to patient matched serum from 7 patients. Interleukin-6 in serum and periprostatic adipose tissue conditioned medium was further analyzed by enzyme-linked immunosorbent assay and correlated with clinical variables, such as age, body mass index and Gleason score, in 45 patients. Interleukin-6 expression in periprostatic adipose tissue was determined by immunohistochemistry. Reverse phase protein microarray technology was used to analyze cell signaling networks in periprostatic adipose tissue. Results: Interleukin-6 in periprostatic adipose tissue conditioned medium was approximately 375 times greater than that in patient matched serum and levels correlated with pathological grade. This finding was further extended by cell signaling analysis of periprostatic adipose tissue, which showed greater phosphorylation on Stat3 with high grade tumors (any component of Gleason score 4 or 5). Conclusions: Higher Gleason score correlated with high levels of conditioned medium derived interleukin-6. Moreover, cell signaling analysis of periprostatic adipose tissue identified activated signaling molecules, including STAT3, that correlated with Gleason score. Since STAT3 is interleukin-6 regulated, these findings suggest that periprostatic adipose tissue may have a role in modulating prostate cancer aggressiveness by serving as a source of interleukin-6. Also, we found low numbers of inflammatory cells in the fat, suggesting that adipocytes are the major secretors of interleukin-6.

Original languageEnglish
Pages (from-to)1621-1627
Number of pages7
JournalJournal of Urology
Volume182
Issue number4 SUPPL.
DOIs
Publication statusPublished - Oct 1 2009
Externally publishedYes

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Adipose Tissue
Interleukin-6
Conditioned Culture Medium
Neoplasm Grading
Adipocytes
Prostatic Neoplasms
Prostate Cancer, Hereditary, 7
Serum
Cytokines
Protein Array Analysis
Prostatectomy
Intercellular Signaling Peptides and Proteins
Body Mass Index
Cell Count
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Phosphorylation
Technology

All Science Journal Classification (ASJC) codes

  • Urology

Cite this

Finley, D. S., Calvert, V. S., Inokuchi, J., Lau, A., Narula, N., Petricoin, E. F., ... Ornstein, D. K. (2009). Periprostatic Adipose Tissue as a Modulator of Prostate Cancer Aggressiveness. Journal of Urology, 182(4 SUPPL.), 1621-1627. https://doi.org/10.1016/j.juro.2009.06.015

Periprostatic Adipose Tissue as a Modulator of Prostate Cancer Aggressiveness. / Finley, David S.; Calvert, Valerie S.; Inokuchi, Junichi; Lau, Alice; Narula, Navneet; Petricoin, Emanuel F.; Zaldivar, Frank; Santos, Rosanne; Tyson, Darren R.; Ornstein, David K.

In: Journal of Urology, Vol. 182, No. 4 SUPPL., 01.10.2009, p. 1621-1627.

Research output: Contribution to journalArticle

Finley, DS, Calvert, VS, Inokuchi, J, Lau, A, Narula, N, Petricoin, EF, Zaldivar, F, Santos, R, Tyson, DR & Ornstein, DK 2009, 'Periprostatic Adipose Tissue as a Modulator of Prostate Cancer Aggressiveness', Journal of Urology, vol. 182, no. 4 SUPPL., pp. 1621-1627. https://doi.org/10.1016/j.juro.2009.06.015
Finley DS, Calvert VS, Inokuchi J, Lau A, Narula N, Petricoin EF et al. Periprostatic Adipose Tissue as a Modulator of Prostate Cancer Aggressiveness. Journal of Urology. 2009 Oct 1;182(4 SUPPL.):1621-1627. https://doi.org/10.1016/j.juro.2009.06.015
Finley, David S. ; Calvert, Valerie S. ; Inokuchi, Junichi ; Lau, Alice ; Narula, Navneet ; Petricoin, Emanuel F. ; Zaldivar, Frank ; Santos, Rosanne ; Tyson, Darren R. ; Ornstein, David K. / Periprostatic Adipose Tissue as a Modulator of Prostate Cancer Aggressiveness. In: Journal of Urology. 2009 ; Vol. 182, No. 4 SUPPL. pp. 1621-1627.
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