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Analysis of the inflammatory network in benign prostate hyperplasia and prostate cancer
Author(s) -
König Jens Ekkehard,
Senge Theodor,
Allhoff Ernst Peter,
König Wolfgang
Publication year - 2003
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.10317
Subject(s) - lncap , prostate cancer , prostate , medicine , chemokine , cytokine , androgen receptor , hyperplasia , angiogenesis , tumor necrosis factor alpha , cancer research , receptor , tramp , androgen , endocrinology , cancer , hormone
The complexity of acute and chronic inflammatory processes may either lead to benign prostate hyperplasia (BPH) and/or prostate cancer. Obviously, various tissue cells are activated by chemokines via different chemotaxin receptors which then trigger subsequent processes in angiogenesis, cellular growth, and extravasation as well as neoplasia. METHODS Using the surgically obtained tissue of patients (n = 36) with BPH or prostate carcinoma (PCA), we studied among others the expression of chemokines (Rantes, IL‐8), chemotaxin receptors (CXCR‐3 and ‐4, CCR‐3, CCR‐5), of matrixmetalloproteinases (MMP‐2 and 9), of Toll‐like (TL) receptors 1, 2, 3, 4, 5, 7, and 9 and of the inducible cyclooxygenase‐2 (cox‐2) by RT‐PCR. Further support for the different properties of tissue from PCA was obtained using two different PCA cell lines (PC3 = androgen resistant cell) or LNCAP cells (androgen sensitive) with emphasis on IL‐8, Il‐6, and PGE 2 release. Cell lines were stimulated with either the tumor necrosis factor‐α (TNF‐α) and lipopolysacharide (LPS) over time. In addition to cytokine release, the quantification of mRNA by lightcycler for cox‐2, IL‐6, and IL‐8 was performed on these cell lines. RESULTS Remarkable differences in expression were obtained by RT‐PCR when BPH tissue versus PCA was analyzed. Expression of CXCR‐1 after incubation with LPS and TNF‐α showed time‐dependent differences for androgen‐sensitive LNCAP as compared to androgen‐resistant PC‐3 cells. TNF‐α incubation leads to a time‐dependent induction of cox‐2 expression unlike to activation with LPS. Differences with regard to cox‐2, IL‐6, and IL‐8 expression were seen by quantitative lightcycler analysis. Significant differences were also observed when TL receptors 4, 5, 7, and 9 were analyzed which were significantly expressed in BPH‐ as compared to PCA‐tissue. CONCLUSIONS Our data clearly demonstrate that various inflammatory and cell biological cascades are involved which either lead to BPH or can be linked to the development of PCA. The exact cell biological mechanisms may provide novel therapeutic options in the treatment of both diseases. © 2003 Wiley‐Liss, Inc.