PMV

Investigating The Effect Of Microparticles (PMVs) On The Growth Of THP-1 Cell Line

Investigating The Effect Of Microparticles (PMVs) On The Growth Of THP-1 Cell Line

Introduction

Platelets are highly reactive components of the circulatory system, which exert not only haemostatic activity but also contribute to the modulation of various pathological conditions including inflammation, atherosclerosis and cancer metastasis through the release of cytokines, chemokines and the presentation of several adhesion molecules. During cancer metastasis, the formation of platelet-tumor cell aggregates in the circulation facilitates immune evasion and the microvascular arrest of tumor cells at distant sites. Several adhesion molecules, such as integrins and glycoproteins, were shown to be involved in this process(Gasic 2009: 99-114). Recent findings indicate that P-selectin is another main mediator of platelet-tumor cell interactions. Other effects of activated platelets on cancer progression are associated with a release of platelet-derived factors stimulating tumor growth and angiogenesis(Karpatkin 2009:1012-1019). Any interference in platelet-tumor cell interactions resulted in attenuation of cancer metastasis. The well recognized, albeit not fully characterized function of platelets during cancer progression defines platelets as potential targets for cancer therapy. Specifically, the rapid expression of P-selectin on the cell surface of activated platelets and its strong association with metastasis provide a rationale for P-selectin inhibition as an antimetastatic treatment.

Discussion

Platelet-derived microvesicles (PMVs) are small fragments shed from the surface of activated platelets and exosomes released from a-granules. PMVs chemoattracted five of six tested lung carcinoma cell lines (human and murine), with especially high effects on the highly metastatic A549 human lung carcinoma cell line and LLC cells. Interaction of the cell lines with PMV in vitro resulted in the activation of MAPK and AKT signaling pathways and an overexpression of cyclin D2, participating in proliferative responses and increased invasiveness of tumor cells. Additionally, mRNA expression of MMP-9 and activation of pro-MMP-2 were increased. Finally, gene upregulation of typical genes involved in tumor vascularization, such as VEGF, IL-8 and scatter factor/hepatocyte growth factor (SF/HGF), was observed. In vivo, PMV covered tumor cells (LLC) were more invasive than controls.

Figure 1. Possible interactions of platelets within the metastatic microenvironment. While tumor cells can induce the initiation of this process, activated platelets can further stimulate leukocytes, endothelium and tumor cells (Karpatkin 2008: 636-641). The ability of platelets to affect various processes including platelet-tumor cell emboli formation, immune-evasion, promotion of tumor cell adhesion and growth, and enhancement of angiogenesis, make platelets a versatile facilitator of metastasis. The functional and temporal roles of platelets during metastasis remain to be characterized.

The main challenge for cancer treatment still remains the control of metastasis. Metastasis is a multistep process initiated by tumor cells that escape from a primary tumor and enter the blood circulation or the lymphatic system. While large numbers of tumor cells may enter the blood stream from a primary lesion, only very few survive the host defense mechanisms, arrest in the vasculature of distant organs and finally form metastatic foci. There is increasing evidence that platelet activity may facilitate this process(Freedman 2008: ...