Adhesive receptors expressed by tumor cells and platelets: novel targets for therapeutic anti-metastatic strategies

Abstract

In vitro and in vivo studies have demonstrated that adhesive interactions between tumor cells and platelets may play a central role in the metastatic process. Ultrastructural studies have demonstrated that platelets appear to enhance the development of arrested tumor emboli into a secondary metastatic colony. Platelet adhesive glycoprotein receptors and their immunorelated counterparts expressed by tumor cells participate in tumor-induced platelet aggregation, which may be an early step in the development of a metastatic lesion. Platelet anti-adhesive agents have been demonstrated to reduce metastases in rodent models. Although tumor adhesive glycoproteins have yet to be fully characterized, specific inhibition of their functional sites could constitute a forthcoming strategy for effective inhibition of metastases.

Surgery for gastric cancer increases plasma levels of vascular endothelial growth factor and von Willebrand factor

“…Plateletpoor plasma obtained with argatroban was collected from 14 patients before surgery (before) and on postoperative day 1 (POD 1), and plasma concentrations of VEGF, sP-selectin, and vWf were determined as described in "Subjects and methods" including intravasation into the bloodstream, adhesion to vascular endothelial cells of distant organs, tumor cell proliferation, and invasion into the target organ. Recent evidence suggests that platelet-tumor and tumor-endothelial interactions participate in the primary adhesive events required for the initiation of the metastatic process [12,19]. vWf and its adhesive ligand, glycoprotein (GP) Ibα on platelets, have been shown to play an important role in the formation of metastasis via tumor-platelet aggregation and thrombus formation [12,20].…”

“…Recent evidence suggests that platelet-tumor and tumor-endothelial interactions participate in the primary adhesive events required for the initiation of the metastatic process [12,19]. vWf and its adhesive ligand, glycoprotein (GP) Ibα on platelets, have been shown to play an important role in the formation of metastasis via tumor-platelet aggregation and thrombus formation [12,20]. P-selectin, an adhesion molecule that mediates interactions of platelets, has also been shown to have a crucial role in developing metastasis [21,22].…”

“…Increased levels of soluble P-selectin (sP-selectin), an adhesion molecule and a component of the membrane of the platelet alpha granule, have been detected in hematological and breast cancers [6], and have been shown to correlate with clinical stage in melanoma [7]. von Willebrand factor (vWf), an adhesive ligand with platelets, has also been shown to be elevated in advanced and disseminated malignancies, such as prostate cancer [8], cervical and ovarian cancer [9], and larynx cancer [10], and it is involved in the metastatic process through the activation of thrombin [11,12].…”

Molecular Identification of Aggrus/T1α as a Platelet Aggregation-inducing Factor Expressed in Colorectal Tumors

“…Activated platelets also induce the formation of a fibrin clot by carrying coagulation factors and providing a catalytic surface for the major interactions of the coagulation cascade. Because there exists a clear link between atherosclerotic vascular disease, inflammation, tumor metastasis, and thrombosis (1)(2)(3), it is important to identify the mechanisms of platelet aggregation that have pathobiologic, prognostic, and treatment-related relevance. Studies on cancer metastasis have shown that some human and animal tumor cells possess platelet aggregation-inducing abilities that correlate with their metastatic potential (2,3).…”

“…Because there exists a clear link between atherosclerotic vascular disease, inflammation, tumor metastasis, and thrombosis (1)(2)(3), it is important to identify the mechanisms of platelet aggregation that have pathobiologic, prognostic, and treatment-related relevance. Studies on cancer metastasis have shown that some human and animal tumor cells possess platelet aggregation-inducing abilities that correlate with their metastatic potential (2,3). Interactions between tumor cells and platelets have been considered to facilitate the arrest of tumor cell cluster in the microcirculation with the subsequent formation of experimental metastasis.…”