Inhibition of Human Tumor Cell Induced Platelet Aggregation by Antibodies to Platelet Glycoproteins lb and llb/llla

Grossi, Irma M.; Fitzgerald, Laurence A.; Kendall, Alan G.; Taylor, John D.; Sloane, B F; Honn, Kenneth V.

doi:10.3181/00379727-186-3-rc1

Cited by 39 publications

(32 citation statements)

References 5 publications

(8 reference statements)

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“…68 Due to its specific expression in MKs and platelets, GPIba could become an attractive target for the development of new skeletal metastasis therapies. However, controversies have been raised in the past for the role of GPIba in tumor cell-induced platelet aggregation, with some reports showing its positive contribution, 69 whereas others described no impact of blocking GPIba antibodies. 70 Also, in an experimental metastasis model using B16F10 melanoma cells, mice lacking GPIba developed a lower number of lung metastases than WT mice, 71 whereas functional inhibition of GPIba using monoclonal antibodies in vivo led to a strong increase in pulmonary metastasis.…”

Section: Platelets Megakaryocytes and Metastasis 27mentioning

confidence: 99%

Metastasis: new functional implications of platelets and megakaryocytes

Leblanc

Peyruchaud

2016

Blood

184

131

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Platelets are essential components of hemostasis. Due to a plethora of factors released on activation, platelet functions are also connected to tumor growth, notably by acting on angiogenesis. It is now well recognized that major roles of platelets in the poor outcome of cancer patients occurs during hematogenous dissemination of cancer cells. In this review, we describe recent insights into the molecular mechanisms supporting the prometastatic activity of platelets. Platelets have been shown to promote survival of circulating tumor cells (CTCs) in the bloodstream by conferring resistance to the shear stress and attack from natural killer cells. Recently, platelets were found to promote and/or maintain the state of epithelial to mesenchymal transition on CTCs through platelet secretion of transforming growth factor β in response to CTC activation. At a later stage in the metastatic process, platelets promote extravasation and establishment of metastatic cells in distant organs as observed in bone. This particular environment is also the site of hematopoiesis, megakaryocytopoiesis, and platelet production. Increasing the number of megakaryocytes (MKs) in the bone marrow results in a high bone mass phenotype and inhibits skeletal metastasis formation of prostate cancer cells. As a result of their specific location in vascular niches in the bone marrow, MK activity might contribute to the “seed and soil” suitability between CTCs and bone. In conclusion, recent findings have made a great advance in our knowledge on how platelets contribute to the metastatic dissemination of cancer cells and that may support the development of new antimetastasis therapies.

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Section: Platelets Megakaryocytes and Metastasis 27mentioning

confidence: 99%

Metastasis: new functional implications of platelets and megakaryocytes

Leblanc

Peyruchaud

2016

Blood

184

131

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“…Similarly, Kitagawa et al [132] demonstrated that the etlIb[33 complex on the platelet surface was involved in both thrombin-dependent and independent platelet aggregations induced by tumor cells. The Gplb may also be important since antibodies to this glycoprotein were shown to inhibit TCIPA [130,132], although different observations were made by Karpatkin et al [133].…”

Section: Formation Of Irreversible Tumor Cell-platelet Aggregatesmentioning

confidence: 99%

“…The potential role of aIIb[33 in TCIPA came to light when Grossi et al [130] and Bastida et al [131] first independently demonstrated that treatment of platelets with antibodies to platelet Gplb or alIb[33 inhibited TCI-PA, suggesting that the platelet ~tlIb[33 integrin receptor is required for TCIPA. These results were subsequently confirmed by others [132,133].…”

Section: Formation Of Irreversible Tumor Cell-platelet Aggregatesmentioning

confidence: 99%

Platelets and cancer metastasis: A causal relationship?

1992

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Cancer metastasis is a highly coordinated and dynamic multistep process in which cancer cells undergo extensive interactions with various host cells before they establish a secondary metastatic colony. Ample morphological studies have documented the close association of circulating tumor cells with host platelets. Several lines of evidence provide strong support for the concept that tumor cell-platelet interactions (i.e., TCIPA) significantly contribute to hematogenous metastasis. Clinically, cancer patients with advanced diseases are characterized by a variety of thromboembolic disorders including thrombocytosis. Pharmacologically, various anti-platelet agents/anticoagulants have demonstrated potent inhibitory effects on tumor cell-platelet interactions as well as spontaneous or experimental metastasis. Experimentally, interference with many of the intermediate steps of tumor cell-platelet interactions has resulted in diminished platelet aggregation induced by tumor cells and blocked cancer metastasis. Platelet interaction with tumor cells is a sequential process which involves two general types of mediators, i.e., membrane-bound molecules (adhesion molecules) and soluble release products. alpha IIb beta 3 integrin receptors present on both platelets as well as on tumor cells and 12(S)-HETE, a 12-lipoxygenase metabolite of arachidonic acid, are prototypical examples of each category. Mechanistically, platelets may contribute to metastasis by: (1) stabilizing tumor cell arrest in the vasculature, (2) stimulating tumor cell proliferation, (3) promoting tumor cells extravasation by potentiating tumor cell-induced endothelial cell retraction, and (4) enhancing tumor cell interaction with the extracellular matrix.

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“…Whereas some groups have not perceived diminished interactions on blockade of GPIb␣, 12 early experiments performed by other groups do suggest a role of GPIb␣ in at least some phases of TCIPA. 37,38 Similarly controversial results have been obtained when GPIb␣ functions in experimental metastasis were studied in vivo. Whereas reduced experimental pulmonary metastasis was observed in mice lacking GPIb␣, 39 functional inhibition of GPIb␣ by monovalent, monoclonal antibodies led to a strong increase in pulmonary melanoma metastasis in vivo 16 (Figure 2).…”

mentioning

confidence: 99%

“…53,54 Of all platelet receptors mentioned in this review, GPIIb/IIIa probably has the longest career as a metastasis-related molecule. As early as 1987, the role of GPIIb/IIIa in TCIPA was established, 37,38 and a year later the importance of this integrin for tumor cell-platelet interactions was shown for several different tumor cell lines, among them 2 colon cancer cell lines as well as B16 melanoma cells (Figure 2) and T241 Lewis bladder cells. 12 In the same publication, the in vivo importance of platelet GPIIb/IIIa in models of pulmonary metastasis was unveiled by blockade of GPIIb/IIIa before tumor cell injection with the monoclonal antibody 10E5.…”

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confidence: 99%

Deadly allies: the fatal interplay between platelets and metastasizing cancer cells

Erpenbeck

Schön

2010

Blood

289

244

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The general notion that functional platelets are important for successful hematogenous tumor metastasis has been inaugurated more than 4 decades ago and has since been corroborated in numerous experimental settings. Thorough IntroductionMetastasis is the main cause of cancer-related death and a major challenge in today's cancer management. Although many new therapies against malignant tumors have been developed over the last years, the prognosis of most malignancies remains unfavorable, once metastatic spread has occurred. This challenge underlines the importance of understanding the details of metastasis to develop specific therapies to impede tumor dissemination.The highly complex process of hematogenous tumor cell spreading includes detachment of cancer cells from the primary site, migration into and transport along the bloodstream, and, finally, tumor cell arrest and proliferation within the distant tissue. Thus, survival of the tumor cells within the bloodstream and adhesion in the vasculature at the metastatic sites are crucial for tumor cell dissemination. There is a plethora of studies indicating that the interaction of tumor cells with platelets within the bloodstream is essential during this early phase of metastasis and that agents directed against specific platelet receptors involved in this process may give rise to new therapies for patients with a high risk of metastasis or for minimizing the risk of cancer cell dissemination during antitumor surgery. Platelets in hematogenous metastasisThe involvement of platelets and coagulation factors in hematogenous tumor metastasis has long been recognized. A relationship between venous thromboembolism and cancer has been observed at least since 1865, 1 and more recent studies have shown that the risk of a diagnosis of cancer is clearly elevated after primary deep venous thromboembolism or pulmonary embolism. 2 As a more direct evidence of platelet involvement in the development of malignant tumors, a relationship between elevated platelet count and malignant tumors was reported by Reiss et al in 1872. 3 So far, thrombocytosis or even platelet counts that are within the upper normal range have been shown to be associated with advanced, often metastatic, stages of cancer and to be a negative prognostic marker for many different tumor entities, including endometrial carcinoma, 4,5 cervical cancer, 6 ovarian cancer, 7 gastric cancer, 8 or esophageal cancer. 9 Clearly, it is difficult to differentiate whether elevated platelet levels actually constitute a predisposition toward a more aggressive disease per se. To our knowledge, there are no prospective studies evaluating the possible development of cancer and aggressive metastatic disease in initially healthy people with elevated platelet levels compared with people with low platelet counts. Although animal models certainly show a role for platelets in cancer metastasis, in patients it is harder to distinguish between a mere correlation between thrombocytosis and cancer and an actual causality. It seems most p...

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Inhibition of Human Tumor Cell Induced Platelet Aggregation by Antibodies to Platelet Glycoproteins lb and llb/llla

Cited by 39 publications

References 5 publications

Metastasis: new functional implications of platelets and megakaryocytes

Metastasis: new functional implications of platelets and megakaryocytes

Platelets and cancer metastasis: A causal relationship?

Deadly allies: the fatal interplay between platelets and metastasizing cancer cells

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