Membrane type‐1 matrix metalloproteinase stimulates tumour cell‐induced platelet aggregation: role of receptor glycoproteins

Abstract

1 Matrix metalloproteinase-2 (MMP-2) plays a role in agonist-and tumour cell-induced platelet aggregation (TCIPA). 2 MMP-2 is synthesized as a proenzyme and is activated at the cell surface by membrane type-1 matrix metalloproteinase (MT1-MMP, MMP-14). 3 The significance of tumour cell-associated MT1-MMP for TCIPA was investigated using human breast carcinoma MCF7 cells stably coexpressing the integrin avb3 with MT1-MMP, cells expressing avb3 alone and mock-transfected cells. 4 Western blot and zymography confirmed that avb3/MT1-MMP cells expressed MT1-MMP and efficiently processed proMMP-2 to MMP-2. 5 Aggregometry, phase-contrast and transmission electron microscopy and flow cytometry were used to characterize TCIPA induced by MCF7 cell lines. 6 The aggregating potency of cells was: avb3/MT1-MMP 4avb3 ¼ mock cells, as shown by aggregometry and phase-contrast microscopy. 7 Electron microscopy revealed close, membrane-membrane interactions between activated platelets and avb3/MT1-MMP cells during TCIPA.

Association of Platelet Count and Platelet Indices with Stages of Women Breast Cancer in Yola, Nigeria

“…Higher circulating platelet count was seen in women with stage 3 and 4 breast cancer than in women with stage 0 and 1 breast cancer (Table 4) this is because cancer cells (which increases with stages of cancer) have been known to stimulate platelet proliferation [32] and this also explains the high platelet count observed in patients with latter (higher) stage of breast cancer compare to that of the control group. High platelet count in cancer was also observed in earlier study by Taucher et al [9] and Sierko et al [10] In addition, adequate platelet count seen in most stages of cancer is believed to promote the mechanism that facilitates the progression of breast cancer [11]. MPV was observed to increases with increase in cancer stage in this present study it is believed that, platelet size as reflected by MPV do increases in direct proportion to breast cancer progression.…”

“…There are reports that thrombocytosis contributes to cancer metastasis [6-,8]. In women with breast cancer, an increased circulating platelet is associated with poor cancer prognosis [9,10], and the ability of breast tumor cells to induce platelet aggregation correlates with their metastatic potential [11]. Studies in breast cancer models have also shown that direct interaction between breast cancer cells and platelets results in the activation of TGF-β (transforming growth factor-beta) signaling pathway, which promotes metastasis, and invasion of cancer cell by inducing epithelial-to-mesenchymal transition and immunosuppression [12,13] and breast cancer cells have been shown to prepares platelets to release pro-angiogenic proteins which stimulate migration and proliferation of cancer cells [14].…”

Non-proteolytic, Receptor/Ligand Interactions Associate Cellular Membrane Type-1 Matrix Metalloproteinase with the Complement Component C1q

“…The binding of membrane-tethered MMPs with C1q is likely to regulate the C1q concentrations in a tumor microenvironment and in the vicinity of malignant cells. These molecular events may be functionally relevant to the subsequent interactions of malignant cells bearing MT-MMPs with the host cells, such as platelets and leukocytes, which express calreticulin/cC1q-R and other types of C1q receptors, which interact with the collagen stalk of C1q (15,16,21,48). Similarly, these events may contribute to the adhesion of metastatic cells to the endothelium and facilitate their transendothelial migration.…”

Haematologic Parameters in Metastatic Colorectal Cancer Patients Treated with Capecitabine Combination Therapy

“…Mevlude Inanc 1 *, Ayse Ocak Duran 2 , Halit Karaca 2 , Veli Berk 2 , Oktay Bozkurt 2 , Ersin Ozaslan 2 , Metin Ozkan 2 potential (Jurasz et al, 2002;Alonso-Escolano et al, 2004). It is well-established that platelets carry a multitude of angiogenesis regulatory proteins in their granules, and the normal ranges of angiogenesis regulators have been characterized in human platelets and in the platelets of patients with malignancy (Peterson et al, 2010).…”