Role of Platelets, Thrombin, Integrin llb-llla, Fibronectin and Von Willebrand Factor on Tumor Adhesion in Vitro and Metastasis in Vivo

Nierodzik, Mary Lynn; Klepfish, Abraham; Karpatkin, Simon

doi:10.1055/s-0038-1642691

Cited by 146 publications

(107 citation statements)

References 47 publications

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“…[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.…”

Section: Discussionmentioning

confidence: 99%

von Willebrand factor expression in osteosarcoma metastasis

et al. 2005

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A number of genes are implicated in the initiation and progression of osteosarcoma; however, cytogenetic and comparative genomic hybridization studies indicate the involvement of additional unidentified genes. An examination of gene expression profiles in 22 high-grade osteosarcoma tumor specimens from 15 patients (including paired primary and metastatic samples from five patients) indicated that von Willebrand factor (vWF) mRNA expression may increase during tumor progression. vWF, a large glycoprotein previously considered to be expressed exclusively by endothelial cells and megakaryocytes, is involved in platelet aggregation and adhesion to the subendothelial matrix, processes critical to hematogenous tumor cell metastasis to the lung. Analysis of paired primary and metastatic osteosarcoma tumor samples from 10 patients revealed an increase in vWF gene expression in metastases (P ¼ 0.005). Immunohistochemistry showed that, in addition to the endothelial cells, vWF protein was also detected in osteosarcoma cells in vivo in 13 of 29 tumor specimens as well as in SAOS2, an osteosarcoma cell line. The tumor cell staining correlated positively with high vWF expression in the sample (P ¼ 0.006). Although vascular endothelial cells contribute to the vWF mRNA detected in the tumor samples, there was neither any correlation between vascular density (VD) and vWF mRNA expression nor between VD and clinical outcome. These findings suggest that vWF expression is deregulated in osteosarcoma tumors, potentially contributing to metastasis.

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Section: Discussionmentioning

confidence: 99%

von Willebrand factor expression in osteosarcoma metastasis

et al. 2005

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“…41 Platelet activation could lead to the release of P-selectin, which, in turn, may facilitate the attachment of tumor cells to the vascular wall. 41 Indeed, plasma levels of P-selectin have been associated with survival and disease recurrences in patients with cancer. 43 The predictive role of P-selectin is supported by our findings (Fig.…”

Section: Discussionmentioning

confidence: 99%

Plasma cytokine and P‐selectin levels in advanced malignancy

Nisio¹,

Niers²,

Reitsma³

et al. 2005

Cancer

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BACKGROUNDThe survival benefit described in patients with cancer treated with low molecular weight heparin (LMWH) may result from a LMWH‐mediated effect on the immune system or on the cross‐talk between platelets and tumor cells.METHODSPlasma levels of interleukin (IL)‐10, IL‐6, interferon (IFN)‐γ, and P‐selectin were measured in patients with advanced stage malignancy who were randomized to receive standard cancer care with or without the addition of LMWH.RESULTSPatients with IL‐6 levels above the median had a median survival of 6.5 months versus 8.8 months for those with values below this cutoff (P = 0.02). IL‐10 levels were found to be similarly correlated with survival such that IL‐10 concentrations above the detection limit of the assay were associated with a doubled risk of dying in comparison to undetectable IL‐10 (P = 0.02). No significant association was found between survival and circulating levels of IFN‐γ. For P‐selectin, patients with values below the fourth quartile had a median survival of 8.8 months versus 6.5 months for patients with levels above the fourth quartile (P = 0.02). In multivariate analysis, IL‐10 remained an independent unfavorable prognostic factor (hazard ratio, 2.13; 95% confidence interval, 1.08–4.20). In patients treated with LMWH, the plasma levels of IL‐6, IL‐10, IFN‐γ, and P‐selectin demonstrated similar correlations with survival. However, none of the markers was associated with the beneficial survival effects observed with the administration of LMWH.CONCLUSIONSIL‐10, IL‐6, and P‐selectin levels predicted a poor outcome in patients with advanced stage malignancy. The prolongation in survival observed with LMWH in patients with cancer apparently cannot be explained by a LMWH effect on these circulating markers. Cancer 2005. © 2005 American Cancer Society.

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“…Fibronectin is involved in cell adhesion and migration processes, including embryogenesis, wound healing, blood coagulation, host defense, and metastasis. [65][66][67][68] Interference with tumor cell binding to fibronectin substrate interferes with cell functions such as adhesiveness, motility, and invasiveness in the cellular adhesive process of metastasis. 67 EDG-1 protein is also highly expressed in endothelial cells, where it binds the ligand sphingosine-1-phosphate, and is suggested to be involved in the processes that regulate differentiation of endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Expression Profiling of Galectin-3-Depleted Melanoma Cells Reveals its Major Role in Melanoma Cell Plasticity and Vasculogenic Mimicry

Mourad-Zeidan

Melnikova

Wang

et al. 2008

The American Journal of Pathology

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Galectin-3 (Gal-3) is a ␤-galactoside-binding protein that is involved in cancer progression and metastasis. Using a progressive human melanoma tissue microarray, we previously demonstrated that melanocytes accumulate Gal-3 during the progression from benign to dysplastic nevi to melanoma and further to metastatic melanoma. Herein, we show that silencing of Gal-3 expression with small hairpin RNA results in a loss of tumorigenic and metastatic potential of melanoma cells. In vitro , Gal-3 silencing resulted in loss of tumor cell invasiveness and capacity to form tube-like structures on collagen ("vasculogenic mimicry"). cDNA microarray analysis after Gal-3 silencing revealed that Gal-3 regulates the expression of multiple genes , including endothelial cell markers that appear to be aberrantly expressed in highly aggressive melanoma cells , causing melanoma cell plasticity. These genes included vascular endothelial-cadherin , which plays a pivotal role in vasculogenic mimicry , as well as interleukin-8 , fibronectin-1 , endothelial differentiation sphingolipid G-protein receptor-1 , and matrix metalloproteinase-2. Chromatin immunoprecipitation assays and promoter analyses revealed that Gal-3 silencing resulted in a decrease of vascular endothelial-cadherin and interleukin-8 promoter activities due to enhanced recruitment of transcription factor early growth response-1. Moreover , transient overexpression of early growth response-1 in C8161-c9 cells resulted in a loss of vascular endothelial-cadherin and interleukin-8 promoter activities and protein expression. Thus , Gal-3 plays an essential role during the acquisition of vasculogenic mimicry and angiogenic properties associated with melanoma progression.

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Role of Platelets, Thrombin, Integrin llb-llla, Fibronectin and Von Willebrand Factor on Tumor Adhesion in Vitro and Metastasis in Vivo

Cited by 146 publications

References 47 publications

von Willebrand factor expression in osteosarcoma metastasis

von Willebrand factor expression in osteosarcoma metastasis

Plasma cytokine and P‐selectin levels in advanced malignancy

Expression Profiling of Galectin-3-Depleted Melanoma Cells Reveals its Major Role in Melanoma Cell Plasticity and Vasculogenic Mimicry

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