Platelet‐derived microparticles promote invasiveness of prostate cancer cells via upregulation of MMP‐2 production

• Published in: International journal of cancer 2009-04, Vol.124 (8), p.1773-1777
• Main Authors: Dashevsky, Olga, Varon, David, Brill, Alexander
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Blood Platelets - metabolism; Cell Adhesion; Cell Culture Techniques - instrumentation; Cycloheximide - pharmacology; Cytoplasm - metabolism; Dactinomycin - pharmacology; Gelatin - chemistry; Gene Expression Regulation, Neoplastic; Humans; Male; Matrix Metalloproteinase 2 - metabolism; Medical sciences; MMP‐2; Nephrology. Urinary tract diseases; platelet‐derived microparticles; prostate cancer; Prostatic Neoplasms - blood; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Protein Synthesis Inhibitors - pharmacology; Time Factors; Tumors; Tumors of the urinary system; Up-Regulation; Urinary tract. Prostate gland
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.24016

Prostate cancer commonly affects men in the Western world. A major factor of the life‐threatening course of this disease is the high rate of metastasis, predominantly to bones. Circulating tumor cells encounter platelets and may activate them, resulting in a production of microparticles (MPs). MPs are small platelet fragments expressing membrane receptors as well as cytoplasmic constituents. Here, we report that prostate cancer cells, Clone‐1 (Cl‐1), preincubated with platelet‐derived MPs (PMPs), demonstrate increased invasion through a gelatin‐coated (a denatured form of collagen) membrane of the Boyden chamber system. This effect was accompanied by an increased secretion of metalloproteinase‐2 (MMP‐2) as demonstrated by a gelatin zymography. Application of MMP‐2/9 inhibitor reversed the PMP‐induced tumor cell invasion. PMPs were shown to adhere to Cl‐1 cells, but direct contact between them may not be mandatory for MMP secretion because PMP lysate induced MMP‐2 production by Cl‐1 cells to the same extent as did intact PMPs. PMP‐induced MMP‐2 secretion was inhibited by neutralization of either PKC or total intracellular tyrosine phosphorylation, but was not affected by blocking major intraplatelet cytokines. Actinomycin D (a transcription inhibitor) did not modify this effect, whereas cycloheximide (an inhibitor of protein translation) abolished the MMP‐2 release. MMP‐2 secretion was accompanied by a rapid and transient increase in MMP‐2 mRNA level after a 2‐hr coincubation of prostate cancer cells with PMPs. Thus, PMPs promote tumor invasiveness, at least in part by stimulation of MMP‐2 production. © 2008 Wiley‐Liss, Inc.