Platelet‐derived microparticles promote invasiveness of prostate cancer cells via upregulation of MMP‐2 production
Open Access
- 12 February 2009
- journal article
- research article
- Published by Wiley in International Journal of Cancer
- Vol. 124 (8), 1773-1777
- https://doi.org/10.1002/ijc.24016
Abstract
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.Keywords
This publication has 26 references indexed in Scilit:
- Lysophosphatidic acid induces prostate cancer PC3 cell migration via activation of LPA1, p42 and p38αBiochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2007
- Lysophosphatidic Acid Down-Regulates Stress Fibers and Up-Regulates Pro–Matrix Metalloproteinase-2 Activation in Ovarian Cancer CellsMolecular Cancer Research, 2007
- Circulating MMP2 and MMP9 in breast cancer—Potential role in classification of patients into low risk, high risk, benign disease and breast cancer categoriesInternational Journal of Cancer, 2006
- Acute Effects of PGF2αon MMP-2 Secretion from Human Ciliary Muscle Cells: A PKC- and ERK-Dependent ProcessPublished by Association for Research in Vision and Ophthalmology (ARVO) ,2005
- Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancerInternational Journal of Cancer, 2004
- Platelet-induced enhancement of LS174T colon carcinoma and THP-1 monocytoid cell adhesion to vascular endothelium under flowAmerican Journal of Physiology-Cell Physiology, 2004
- The functional role of blood platelet components in angiogenesisThrombosis and Haemostasis, 2004
- Role of angiogenesis in tumor growth and metastasisSeminars in Oncology, 2002
- Platelets mediate tumor cell adhesion to the subendothelium under flow conditions: Involvement of platelet GPIIb-IIIa and tumor cell ?v integrinsInternational Journal of Cancer, 1997
- Antimetastatic effects associated with platelet reduction.Proceedings of the National Academy of Sciences, 1968