Platelet-derived thrombospondin-1 is a critical negative regulator and potential biomarker of angiogenesis

Zaslavsky, Alexander; Baek, Kwan-Hyuck; Lynch, Ryan C.; Short, Sarah M.; Grillo, Jenny; Folkman, Judah; Italiano, Joseph E.; Ryeom, Sandra

doi:10.1182/blood-2009-09-242065

Cited by 164 publications

(144 citation statements)

References 48 publications

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“…However, thrombocytopenia had no effect on angiogenesis at a later stage when the angiogenic islets had developed into invasive carcinomas (Ringvall et al, 2011). In addition, negative regulation of angiogenesis by platelet-derived TSP was demonstrated to play a role during early stages of tumor vascularization (Zaslavsky et al, 2010). Together these data support a role for platelets early in the angiogenic process.…”

Section: The Role Of Platelets In Tumor Angiogenesis and Growthsupporting

confidence: 58%

Platelet Regulation of Angiogenesis, Tumor Growth and Metastasis

Cedervall¹,

Olsson²

2012

Tumor Angiogenesis

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Section: The Role Of Platelets In Tumor Angiogenesis and Growthsupporting

confidence: 58%

Platelet Regulation of Angiogenesis, Tumor Growth and Metastasis

Cedervall¹,

Olsson²

2012

Tumor Angiogenesis

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“…To support this, megakaryocytes have been reported to increase their number in response to cancer bone metastasis and inhibit prostate and breast cancer cell growth both in vitro and in vivo (48)(49)(50). Although the prognostic value and biological functions of megakaryocytes in cancer development and progression need to be further investigated, models that analyze the number difference between CTCs and megakaryocytes should be developed to make an efficient biomarker for survival prediction for patients with mCRPCs and potentially for other cancers as well.…”

Section: Discussionmentioning

confidence: 99%

The Novel Association of Circulating Tumor Cells and Circulating Megakaryocytes with Prostate Cancer Prognosis

Mao

Guo

et al. 2017

Clinical Cancer Research

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Purpose: To develop an approach for the investigation of different subtypes of circulating tumor cells (CTC) and other cells to evaluate their potential prognostic value of prostate cancer.Experimental Design: Malignancy of CTCs undergoing epithelial-to-mesenchymal transition (EMT) was confirmed by repeated FISH. Subgroups of CTCs in 81 patients with prostate cancer (43 castration resistant and 38 untreated localized) were correlated to disease aggressiveness parameters. AUC analysis was applied to compare the performance for metastasis prediction between serum PSA level alone and a combined risk score using both PSA and EMTing CTC count. Circulating megakaryocytes and cancer patient survival association was performed using Cox model.Results 0).Conclusions: This CTC analysis approach and the potential association of megakaryocytes with cancer prognosis may greatly enhance our ability to investigate the cancer metastasis process and to predict/monitor cancer progression.

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“…Interestingly, patients with metastatic disease reveal increased platelet counts and significantly elevated numbers of activated platelets (12). Depending on the type of tumor, various aspects of cancer progression may be affected by platelets, including tumor cell proliferation (13), tumor angiogenesis (14), vessel stability within tumors (15), or immune evasion (16,17). Moreover, platelets contribute to a specific gene expression profile of microvascular endothelial cells in the presence of tumor cells and consecutively to a permissive metastatic microenvironment (18).…”

mentioning

confidence: 99%

Engagement of αIIbβ3 (GPIIb/IIIa) with ανβ3 Integrin Mediates Interaction of Melanoma Cells with Platelets

Lonsdorf

Kramer

Fahrleitner

et al. 2012

Journal of Biological Chemistry

100

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A mutual relationship exists between metastasizing tumor cells and components of the coagulation cascade. The exact mechanisms as to how platelets influence blood-borne metastasis, however, remain poorly understood. Here, we used murine B16 melanoma cells to observe functional aspects of how platelets contribute to the process of hematogenous metastasis. We found that platelets interfere with a distinct step of the metastasis cascade, as they promote adhesion of melanoma cells to the endothelium in vitro under shear conditions. Constitutively active platelet receptor GPIIb/IIIa (integrin ␣IIb␤3) expressed on Chinese hamster ovary cells promoted melanoma cell adhesion in the presence of fibrinogen, whereas blocking antibodies to a␤3 integrin on melanoma cells or to GPIIb/IIIa significantly reduced melanoma cell adhesion to platelets. Furthermore, using intravital microscopy, we observed functional platelet-melanoma cell interactions, as platelet depletion resulted in significantly reduced melanoma cell adhesion to the injured vascular wall in vivo. Using a mouse model of hematogenous metastasis to the lung, we observed decreased metastasis of B16 melanoma cells to the lung by treatment with a mAb blocking the a subunit of a␤3 integrin. This effect was significantly reduced when platelets were depleted in vivo. Thus, the engagement of GPIIb/IIIa with a␤3 integrin interaction mediates tumor cell-platelet interactions and highlights how this interaction is involved in hematogenous tumor metastasis.

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Platelet-derived thrombospondin-1 is a critical negative regulator and potential biomarker of angiogenesis

Cited by 164 publications

References 48 publications

Platelet Regulation of Angiogenesis, Tumor Growth and Metastasis

Platelet Regulation of Angiogenesis, Tumor Growth and Metastasis

The Novel Association of Circulating Tumor Cells and Circulating Megakaryocytes with Prostate Cancer Prognosis

Engagement of αIIbβ3 (GPIIb/IIIa) with ανβ3 Integrin Mediates Interaction of Melanoma Cells with Platelets

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