The Arg-Gly-Asp-containing peptide, rhodostomin, inhibits in vitro cell adhesion to extracellular matrices and platelet aggregation caused by saos-2 human osteosarcoma cells

Abstract

Sumary Saos-2 cells, derived from a primary human osteosarcoma, caused dose-dependent platelet aggregation in heparinised human platelet-rich plasma. Saos-2 tumour cell-induced platelet aggregation (TCIPA) was completely inhibited by hirudin but unaffected by apyrase. The cell suspension shortened the plasma recalcification times of normal, factor VIII-deficient and factor IX-deficient human plasmas in a dosedependent manner. However, the cell suspension did not affect the recalcification time of factor VII-deficient plasma. Moreover, a monoclonal antibody (MAb) against human tissue factor completely abolished TCIPA. Flow cytometric analysis using anti-integrin MAbs as the primary binding ligands demonstrated that the integrin receptors cvP3, 1 and ae8B were present on the surface of Saos-2 cells, which might mediate tumour cell adhesion to extracellular matrix. Rhodostomin, an Arg-Gly-Asp (RGD)-containing snake venom peptide which antagonises the binding of fibnrnogen to platelet membrane glycoprotein i1b/i11a, prevented Saos-2 TCIPA as well as tumour cell adhesion to vitronectin, fibronectin and collagen type I. Likewise, the synthetic peptide Gly-Arg-Gly-Asp-Ser (GRGDS) showed a similar effect. On a molar basis, rhodostomin was about 18 000 and 1000 times. respectively, more potent than GRGDS in inhibiting TCIPA and tumour cell adhesion.

von Willebrand factor expression in osteosarcoma metastasis

“…[16][17][18] Pretreatment of either tumor cells or platelets with an antibody or peptide that neutralizes vWF or blocks vWF-capable receptors (eg integrins GPIIb/ IIIa and GPIb-present on numerous tumor cell lines) has been shown to inhibit tumor cell-platelet interaction in vitro for colon carcinoma, Walker 256 carcinosarcoma, melanoma and osteosarcoma cell lines (including SAOS2). 19,[44][45][46][47][48][49][50][51][52] Notably, treatment with monoclonal anti-vWF antibody significantly decreased tumor cell metastases in vivo for colon, Lewis bladder and melanoma carcinoma cell 53 suggested that this tumor cell-platelet mechanism may be partially responsible for the common metastasis of osteosarcoma to the lung. In support of this, the osteosarcoma cell lines MG63, HOS, U2-OS, TE-85 and SAOS2 have been shown to induce platelet aggregation.…”

“…In support of this, the osteosarcoma cell lines MG63, HOS, U2-OS, TE-85 and SAOS2 have been shown to induce platelet aggregation. 46,[53][54][55] The vWF produced by SAOS2 may contribute to its ability to aggregate platelets. vWF expression by osteosarcoma tumor cells may contribute to tumor cell-platelet aggregation as well as tumor-subendothelium adhesion, increasing the likelihood of successful blood-borne metastasis to the lung.…”

Serum amyloid A mediates the inhibitory effect of Ganoderma lucidum polysaccharides on tumor cell adhesion to endothelial cells

“…One possible explanation may be related to the functional adhesion motifs of SAA. According to previous reports, some proteins containing the peptide Tyr-IIe-GlySer-Arg (YIGSR) and/or Arg-Gly-Asp (RGD) demonstrated inhibition activities in tumor cell invasion and metastasis, such as the multimeric YIGSR-containing peptide (Ac-Y16), and RGD-containing peptide (rhodostomin) (29)(30)(31). Both functional YIGSR-like and RGD-like motifs also present in the SAA protein (22).…”

Cooperation of protease-activated receptor 1 and integrin ανβ5 in thrombin-mediated lung cancer cell invasion

“…Thrombin can affect the expression or distribution of integrins on the tumor cell surface (15)(16)(17). The Arg-Gly-Asp (RGD)-containing snake venom peptide and synthetic peptides can block thrombin-mediated tumor cell adhesion (15,18). However, the mechanism by which thrombin activates integrins has not yet been clearly described.…”