Tumor‐cell‐induced platelet aggregation is a glycoprotein‐dependent and lipoxygenase‐associated process

Bastida, E; Almirall, L; Ordinas, Antonio

doi:10.1002/ijc.2910390617

Cited by 53 publications

(43 citation statements)

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“…6,[32][33][34][35][36] Our observation that MCF-7 tumor cells promote the differential release of pro-angiogenic proteins from platelets may explain why some of the inhibitors of platelet function, including aspirin and other antiplatelet agents can interfere with tumor metastasis and growth. 12,[37][38][39][40] By understanding the mechanisms involved in specific types of tumor cell-induced platelet activation (TCIPA) we can better target platelet agents that may be beneficial for decreasing angiogenesis and limiting tumor growth and metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…Aspirin also functions as an inhibitor of TCIPA in vitro. 12,[37][38][39][40] Yet another mechanism by which aspirin could modulate cancer is as an irreversible inhibitor of platelet activation with subsequent decrease in VEGF release and decrease in angiogenic potential as shown in "Aspirin inhibits the release of VEGF from platelets and suppresses angiogenesis mediated by MCF-7 cells or ADP." These anti-metastatic effects are not limited to aspirin as other antiplatelet agents such as P2Y 12 and GPII/IIIa antagonists also inhibit TCIPA.…”

Section: Discussionmentioning

confidence: 99%

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Release of angiogenesis regulatory proteins from platelet alpha granules: modulation of physiologic and pathologic angiogenesis

Battinelli

Markens

Italiano

2011

Blood

328

290

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Release of angiogenesis regulatory proteins from platelet alpha granules: modulation of physiologic and pathologic angiogenesis

Battinelli

Markens

Italiano

2011

Blood

328

290

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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

292

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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“…Bastida et al (1987) and Grossi et al (1987) first reported inhibition of platelet aggregation induced by human tumor cells following treatment of PRP with polyclonal and monoclonal antibodies to human all&.…”

Section: Discussionmentioning

confidence: 97%

Studies on the role of platelet eicosanoid metabolism and integrin α_IIbβ₃ in tumor‐cell‐induced platelet aggregation

Steinert

Tang

Grossi

et al. 1993

Intl Journal of Cancer

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Platelet eicosanoid metabolism resulting from tumor-cell-induced platelet aggregation (TCIPA) was examined in a homologous in vitro system. Rat Walker 256 carcinosarcoma cells induced the aggregation of rat platelets via a thrombin-dependent mechanism with concomitant production of eicosanoid metabolites (e.g., 12-HETE, TXA2). TCIPA was dependent on the concentration of tumor cells inducing aggregation, as well as cyclooxygenase and lipoxygenase products. Cyclooxygenase inhibitors, but not lipoxygenase inhibitors, blocked platelet aggregation induced in vitro by a low concentration of agonist. At a high agonist concentration, neither cyclooxygenase nor lipoxygenase inhibitors alone affected platelet aggregation; however, the combined inhibition of both the cyclooxygenase and lipoxygenase pathways resulted in subsequent inhibition of platelet aggregation regardless of agonist concentration. The extent of platelet TXA2 and 12-HETE biosynthesis was likewise dependent on and correlated with agonist concentration. The inhibitors used in this study did not significantly inhibit protein kinase C activity at the doses tested. Platelet surface glycoprotein alpha IIb beta 3 play an important role in platelet aggregation. The effect of platelet cyclooxygenase and lipoxygenase inhibition in regulating alpha IIb beta 3 surface expression was examined by flow cytometric analysis. Thrombin stimulation of washed rat platelets resulted in significantly increased surface expression of platelet alpha IIb beta 3 integrin complex. The enhanced surface expression was not inhibited by a cyclooxygenase inhibitor (aspirin), a thromboxane synthase inhibitor (CGS-14854) or a thromboxane receptor antagonist (SQ 29,548), nor was it stimulated by a thromboxane A2 mimic (pinane-thromboxane A2). However, alpha IIb beta 3 expression was blocked by lipoxygenase inhibition and stereospecifically increased by the platelet lipoxygenase metabolite 12(S)-HETE. These results suggest that both the platelet lipoxygenase and cyclooxygenase pathways are important for TCIPA but that different mechanisms of action are involved.

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Tumor‐cell‐induced platelet aggregation is a glycoprotein‐dependent and lipoxygenase‐associated process

Cited by 53 publications

References 16 publications

Release of angiogenesis regulatory proteins from platelet alpha granules: modulation of physiologic and pathologic angiogenesis

Release of angiogenesis regulatory proteins from platelet alpha granules: modulation of physiologic and pathologic angiogenesis

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

Studies on the role of platelet eicosanoid metabolism and integrin α_IIbβ₃ in tumor‐cell‐induced platelet aggregation

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Tumor‐cell‐induced platelet aggregation is a glycoprotein‐dependent and lipoxygenase‐associated process

Cited by 53 publications

References 16 publications

Release of angiogenesis regulatory proteins from platelet alpha granules: modulation of physiologic and pathologic angiogenesis

Release of angiogenesis regulatory proteins from platelet alpha granules: modulation of physiologic and pathologic angiogenesis

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

Studies on the role of platelet eicosanoid metabolism and integrin αIIbβ3 in tumor‐cell‐induced platelet aggregation

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Studies on the role of platelet eicosanoid metabolism and integrin α_IIbβ₃ in tumor‐cell‐induced platelet aggregation