Enhancing effect of platelet-derived microvesicles on the invasive potential of breast cancer cells

Platelets (PLTs) have been postulated to play a role in cancer progression and metastasis. Recently, it was demonstrated that PLT-derived microvesicles (PMVs) transfer various surface receptors and/or adhesion molecules to target cells and modulate their biological responses. In this work, it was hypothesized that PMVs interact with breast cancer cells, increasing their invasiveness. PMVs (isolated from outdated PLT concentrates) were incubated with three human breast cancer cell lines (MDA-MB-231, BT-549, and T47D), and their effects on in vitro invasiveness of these cells (adhesion, expression of matrix metalloproteinases [MMPs], and chemoinvasion), as well as their interactions with stroma, were evaluated. We found that PMVs 1) transferred PLT-derived integrin CD41 to the surface of breast cancer cells and enhanced their adhesion to endothelial cells; 2) increased CXCR4 expression and chemotaxis toward a stromal-derived factor-1 gradient in invasive MDA-231 and BT-549 cells; 3) increased phosphorylation of the mitogen-activated protein kinase p42/44 and AKT signaling pathways; 4) stimulated the production of MMPs in invasive MDA-231 and BT-549 cells and their chemoinvasion across the reconstituted basement membrane Matrigel; and 5) induced the secretion of MMP-9 by marrow fibroblasts and stimulated the secretion of both MMP-2 and MMP-9 in cocultures of fibroblasts with MDA-MB-231 cells. It was shown than PMVs enhance the in vitro invasive potential of invasive breast cancer cell lines and therefore could mediate the progression of breast cancer. These findings warrant further evaluation of the implications of PLT transfusions in cancer patients.