Platelet‐derived growth factor induces proliferation of hyperplastic human prostatic stromal cells

Abstract

Prostatic hyperplasia (BPH) is a very common disease in elderly men and is characterized by abnormal proliferation of the stromal and epithelial cells of the prostate. The observation that BPH often occurs in association with chronic inflammation has led to the examination of the possibility that platelet-derived growth factor (PDGF), which is released in response to inflammation, may be an etiological factor in the genesis of the disease. It has been shown that cultured cells derived from human prostatic tissue express high affinity PDGF-beta receptors based on receptor binding and cross-linking studies with [125I]-PDGF-BB. The experiments presented below demonstrate that PDGF receptors are activated in response to the growth factor and that mitogenesis is induced. PDGF-BB treatment of cultured human prostate cells derived from patients with BPH activates the signal transduction pathway of the PDGF receptor as shown by the presence of several phosphoproteins in antiphosphotyrosine immunoprecipitates, including autophosphorylation of the PDGF receptor. Phosphatidylinositol (PI) 3-kinase activity is also increased in cells stimulated with PDGF. The addition of PDGF-BB to the medium causes of variable but dose-dependent increase in [3H]-thymidine incorporation. This paper describes the first demonstration that PDGF is a potent mitogen for human cells derived from patients exhibiting prostatic hyperplasia, and also demonstrates that the cellular response to PDGF-BB is heterogenous in a manner that is consistent with the varying degree of hyperplasia and inflammation clinically and histologically in the tissue specimens.

Stimulation of Hyaluronan Synthetase by Platelet-Derived Growth Factor bb in Human Prostate Smooth Muscle Cells

“…PDGFbb has been shown to induce proliferation of prostate stromal cells [17,22]. Our data demonstrate that the production of HA, an important extracellular matrix component, is higher in cells from patients with BPH and that their cells are more responsive to PDGFbb.…”

“…The stromal cells from prostate display high affinity PDGFbb receptors and exposure of these cells to PDGFbb leads to proliferation [17].…”

PSK, a Novel STE20-like Kinase Derived from Prostatic Carcinoma That Activates the c-Jun N-terminal Kinase Mitogen-activated Protein Kinase Pathway and Regulates Actin Cytoskeletal Organization

“…The presence of IGF1-R in all three of our screened prostatic carcinoma tissues supports the notion that IGF1-R may play a functional role in prostate cancer development. We also detected a number of other receptor kinases in our degenerate PCR screen of prostatic carcinoma tissues including PDGFBR; PDGF acts as a potent mitogen for prostate cells (60) and the oncogenic potential of PDGFBRs has been well characterized in other cancers. VEGFR2 and the HGF receptor c-MET also function to regulate cell growth, migration, and the actin cytoskeleton via autocrine and paracrine loops, and increases in expression of both vascular EGF and c-MET proteins have been reported in malignant prostate cells (61)(62)(63).…”

Shrinkage of Prostate Volume in Sunitinib-treated Patients with Renal Cell Carcinoma

“…Since VEGF and PDGF are the most potent mitogenic factors stimulating both endothelial and epithelial cells in a normal prostate gland (11,12), reduction in prostate volume might be caused by the inhibition of VEGF and PDGF receptors. A recent report has shown a marked reduction in the thyroid gland by sunitinib (9,13).…”