Role of tumor cell glycoproteins immunologically related to glycoproteins Ib and IIb/IIIa in tumor cell‐platelet and tumor cell‐matrix interactions

Grossi, Irma M.; Hatfield, James S.; Fitzgerald, Laurence A.; Newcombe, Marcia; Taylor, John D.; Honn, Kenneth V.

doi:10.1096/fasebj.2.8.2452113

Cited by 90 publications

(51 citation statements)

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“…In order to identify a potential counter receptor for platelet integrin ␣IIb␤3 expressed by the melanoma cells, we reasoned that ␣IIb␤3 may bind to a related receptor expressed by the melanoma cell using a mechanism similar to that which governs platelet-platelet interaction in thrombus formation. Evidence suggests that an ␣IIb␤3-related integrin expressed by tumor cells might be involved in their interaction with platelets (46,47). This ␣IIb␤3-related molecule may represent tumor cell integrin ␣v␤3, since these receptors share characteristic homologies and a ligand recognition repertoire.…”

Section: Discussionmentioning

confidence: 99%

Role of β3 Integrins in Melanoma Cell Adhesion to Activated Platelets under Flow

Felding-Habermann

Habermann

Saldı́var

et al. 1996

Journal of Biological Chemistry

151

149

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Mechanisms mediating tumor cell attachment to the vessel wall under flow conditions are largely unknown. Therefore we analyzed the ability of human melanoma cells to adhere to an immobilized matrix during blood flow and determined the role of platelets in this process. In a parallel plate flow chamber, M21 melanoma cells were suspended in human blood and perfused over a collagen I matrix at a wall shear rate of 50 s ؊1 (2 dynes/ cm 2 ) to simulate venous flow over a thrombogenic surface. Melanoma cell interaction with the matrix or blood cells and platelets was monitored and quantified by fluorescence and confocal laser microscopy. Despite their ability to adhere to collagen I under static conditions, M21 cells failed to attach directly to this matrix during blood flow. However, they associated with adherent thrombi, and this resulted in stable melanoma cell arrest. Inhibition of platelet activation or platelet integrin ␣IIb␤3 function abolished M21 cell attachment. Melanoma cell interaction with thrombi was specific and required ␤3 integrin expression. M21-L cells which lack integrin ␣v␤3 failed to associate with thrombi and to arrest during blood flow. Transfection of these cells with the integrin subunits ␣v or ␣IIb resulted in variants expressing ␣v␤3, as in the wild type, or ␣IIb␤3. Both variants were able to associate with thrombi and to arrest during blood flow. Therefore, ␤3 integrin-mediated binding to activated platelets represents an efficient mechanism for melanoma cell arrest under flow, and this may contribute to the role of platelets in hematogenous metastasis.

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Section: Discussionmentioning

confidence: 99%

Role of β3 Integrins in Melanoma Cell Adhesion to Activated Platelets under Flow

Felding-Habermann

Habermann

Saldı́var

et al. 1996

Journal of Biological Chemistry

151

149

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“…The tumor cells employed in this study as well as our previous report (4) bind to fibronectin or von Willebrand factor.2 Similar binding ofa human melanoma cell to fibronectin and von Willebrand factor has recently been reported (25). Employing a human melanoma cell line (SK-MEL-28) that binds to platelets, we have identified receptors for fibronectin (a3#l1) and vitronectin (a,#3) by fluorescence flow cytometry, employing monoclonal antibodies specific for these receptors or their subunits (A. Klepfish and S. Karpatkin, unpublished data).3 An immunologically related GPIIb-GPIIIa complex has recently been reported for two human cell lines (cervical carcinoma, MS751 and colon carcinoma, clone A) that is required for binding to fibronectin (31). (b) Fibronectin and von Willebrand factor are anchored to the platelet by the platelet integrin GPIIb-GPIIIa (5, 6).…”

Section: Discussionmentioning

confidence: 99%

Thrombin stimulates tumor-platelet adhesion in vitro and metastasis in vivo.

Nierodzik¹,

Plotkin²,

Kajumo³

et al. 1991

J. Clin. Invest.

232

157

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Recent studies have revealed a role for platelets and the platelet-adhesive proteins, fibronectin and von Willebrand factor (vWF) in platelet-tumor cell interaction in vitro and metastasis in vivo. The present report documents the effect of thrombin treatment of platelets on this interaction in vitro and in vivo. In vitro, thrombin at 100-1,000 mU/ml maximally stimulated the adhesion of six different tumor cell lines from three different species two-to fivefold. As little as 1-10 mU/ml was effective. The effect of thrombin was specific (inhibitable by hirudin, dansyl-arginine N43-ethyl-1,5 pentanediyl) amide and unreactive with the inactive thrombin analogue N-P-tosyl-L-phenylchloromethylketone-thrombin and D-phenylalanyl-L-propyl-L-arginine chloromethylketone-thrombin (PPACK-thrombin), and required high-affinity thrombin receptors (competition with PPACK-thrombin but not with N-P-tosyl-L-lysine-chloromethyl-ketone-thrombin). Functionally active thrombin was required on the platelet surface. Binding of tumor cells to thrombin-activated platelets was inhibitable by agents known to interfere with the platelet GPIIb-GPIIIa integrin: monoclonal antibody 10E5, tetrapeptide RGDS and 'y chain fibrinogen decapeptide LGGAKQAGDV, as well as polyclonal antibodies against the platelet adhesive ligands, fibronectin and vWF. In vivo, thrombin at 250-500 mU per animal increased murine pulmonary metastases fourfold with CT26 colon carcinoma cells and 68-413-fold with B16 amelanotic melanoma cells. Thus, thrombin amplifies tumor-platelet adhesion in vitro twoto fivefold via occupancy of high-affinity platelet thrombin receptors, and modulation of GPIIb-GPIIIa adhesion via an RGD-dependent mechanism. In vivo, thrombin enhances tumor metastases 4-413-fold with two different tumor cells lines. (J. Clin. Invest. 1991. 87:229-236.).

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“…GPIb is also constitutively expressed in platelets, and its main role is to attach platelets to the injured part of the vascular wall (Ruggeri, 1999). Both GPIIb/IIIa and GPIb have been implicated in tumor cell-platelet interactions and subsequent tumor metastasis since colon carcinoma cells pretreated with antibodies against platelet GPIb and/or GPIIb/IIIa inhibited their ability to induce platelet aggregation (Grossi et al, 1988). P-selectin is mainly stored in platelet ␣-granules, and upon platelet activation, this receptor is translocated to the platelet surface mediating leukocyte rolling and the formation of platelet-leukocyte aggregates (Andrews and Berndt, 2004).…”

Section: Tcipa In Caco-2 743mentioning

confidence: 99%

Platelet Aggregation-Induced by Caco-2 Cells: Regulation by Matrix Metalloproteinase-2 and Adenosine Diphosphate

Medina¹,

Jurasz²,

Santos-Martínez³

et al. 2006

J Pharmacol Exp Ther

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Formation of tumor cell-platelet aggregates facilitates hematogenous metastases. However, molecular mechanisms implicated in tumor cell-induced platelet aggregation (TCIPA) in colon cancer are unclear. To investigate mechanisms of TCIPA induced by colon adenocarcinoma cells in vitro, human Caco-2 cells were used to study their interactions with platelets using aggregometry, zymography, phase-contrast microscopy, and flow cytometry. Caco-2-induced platelet aggregation in a concentration-dependent manner. This aggregation resulted in the release of matrix metalloproteinase (MMP)-2, as measured by zymography. In addition, flow cytometry showed a significant up-regulation of activated GpIIb/IIIa, total GpIIb/IIIa, GpIb, and P-selectin receptors on platelets. Inhibition of MMP-2 by phenantroline and degradation of ADP by APT102, respectively, resulted in inhibition of TCIPA. Furthermore, both phenantroline and APT102 significantly down-regulated the surface abundance of platelet receptors. Caco-2 cells aggregate platelets, at least in part, via releasing MMP-2 and ADP. Modulation of MMP-2 and ADP actions could have therapeutic value in colonic cancer.

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Role of tumor cell glycoproteins immunologically related to glycoproteins Ib and IIb/IIIa in tumor cell‐platelet and tumor cell‐matrix interactions

Cited by 90 publications

References 0 publications

Role of β3 Integrins in Melanoma Cell Adhesion to Activated Platelets under Flow

Role of β3 Integrins in Melanoma Cell Adhesion to Activated Platelets under Flow

Thrombin stimulates tumor-platelet adhesion in vitro and metastasis in vivo.

Platelet Aggregation-Induced by Caco-2 Cells: Regulation by Matrix Metalloproteinase-2 and Adenosine Diphosphate

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