Thrombin as a survival factor for cancer cells: thrombin activation in malignant effusions in vivo and inhibition of idarubicin-induced cell death in vitro

Schiller, H.; Bartscht, Tobias; Arlt, Alexander; Zahn, Michael; Seifert, Anja; Bruhn, Thomas; Bruhn, H. D.; Gieseler, Frank

doi:10.5414/cpp40329

Cited by 36 publications

(23 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To date, four subtypes of PAR have been identified in humans (named PAR1 to PAR4), whose expression has been detected in most tissues and in numerous cells. 9 In hematological malignancies, PAR3 has been shown to be upregulated by the induction of megakaryocyte phenotype in human erythroleukemia cells, 10 and PAR1 expression has been verified by flow cytometry analysis in the promyelocytic cell line HL-60, 11 and after induced differentiation in the monocytic cell line U937. 12 Recent studies have shown that the TF-VII(a) complex activates PAR2, and the product of initiation of coagulation, Xa, while still assembled in the transient ternary TF-VII(a)-Xa complex, signals through PAR1 or PAR2.…”

Section: Tf/fvii(a)-induced Intracellular Signalingmentioning

confidence: 91%

Tissue factor as an effector of angiogenesis and tumor progression in hematological malignancies

et al. 2006

View full text Add to dashboard Cite

Section: Tf/fvii(a)-induced Intracellular Signalingmentioning

confidence: 91%

Tissue factor as an effector of angiogenesis and tumor progression in hematological malignancies

et al. 2006

View full text Add to dashboard Cite

“…Furthermore, thrombin is discussed to have a hormone like function causing the activation of growth factor receptors (Hollenberg and Houle 2005). It is supposed to be a survival factor for cancer cells (Schiller et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Expression of proteinase-activated receptor 1-4 (PAR 1-4) in human cancer

Elste

Petersen

2010

J Mol Hist

View full text Add to dashboard Cite

Proteinase activated receptors (PAR 1-4) are membrane receptors with a unique way of activation by proteinases like thrombin, trypsin and matrix metalloproteinases which lead to a specific cellular response. To evaluate the significance of expression and co-expression of PAR in cancer we performed a survey on published data. A Pubmed literature search on "PAR, thrombin, cancer" was performed and 46 publications were selected for systematic review based on the availability of information on tumor type, material type, detection method and specification of positive cases. PAR-1 was found in 77.3% of malignant samples (n = 678), PAR-2 in 79.5% (n = 592), PAR-3 in 12.6% (n = 87) and PAR-4 in 54.9% (n = 153). PAR-1 and -2 were present in adenocarcinomas, melanomas, osteosarcomas, glioblastomas, meningiomas, leukaemias and squamous cell carcinomas. Presence of PAR-3 was limited to kidney and liver cancer. The data on PAR-4 expression was inconclusive. Those studies analysing PAR-1 and PAR-2 reported coexpression of the two receptors. PAR-1 and -2 are widely expressed in human tumors suggesting an important role in tumorigenesis and providing potential targets for therapy. PAR-3 and PAR-4 are less frequently detectable, their expression and potential role in tumorigenesis require further investigation.

show abstract

“…Fibrinopeptide A, a marker of thrombin generation, was elevated in patients with leukemia, nonHodgkin's lymphoma, and solid tumors. Thrombin pretreatment of cell lines from these cancer types completely abrogated the induction of apoptosis by chemotherapy [83]. Moreover, mice transplanted with human ovarian cancer cells (SKOV3) demonstrated larger tumor size and decreased survival rate when treated with thrombin [82].…”

Section: Tumor Cellsmentioning

confidence: 98%

“…Thrombin also serves as a pro-survival factor for cancer cells [16,82,83]. Fibrinopeptide A, a marker of thrombin generation, was elevated in patients with leukemia, nonHodgkin's lymphoma, and solid tumors.…”

Section: Tumor Cellsmentioning

confidence: 99%

Thrombin—unique coagulation system protein with multifaceted impacts on cancer and metastasis

Wojtukiewicz

Hempel

Sierko

et al. 2016

Cancer Metastasis Rev

View full text Add to dashboard Cite

The association between blood coagulation and cancer development is well recognized. Thrombin, the pleiotropic enzyme best known for its contribution to fibrin formation and platelet aggregation during vascular hemostasis, may also trigger cellular events through protease-activated receptors, PAR-1 and PAR-4, leading to cancer progression. Our pioneering findings provided evidence that thrombin contributes to cancer metastasis by increasing adhesive potential of malignant cells. However, there is evidence that thrombin regulates every step of cancer dissemination: (1) cancer cell invasion, detachment from primary tumor, migration; (2) entering the blood vessel; (3) surviving in vasculature; (4) extravasation; (5) implantation in host organs. Recent studies have provided new molecular data about thrombin generation in cancer patients and the mechanisms by which thrombin contributes to transendothelial migration, platelet/tumor cell interactions, angiogenesis, and other processes. Though a great deal is known regarding the role of thrombin in cancer dissemination, there are new data for multiple thrombin-mediated events that justify devoting focus to this topic with a comprehensive approach.

show abstract

Thrombin as a survival factor for cancer cells: thrombin activation in malignant effusions in vivo and inhibition of idarubicin-induced cell death in vitro

Cited by 36 publications

References 0 publications

Tissue factor as an effector of angiogenesis and tumor progression in hematological malignancies

Tissue factor as an effector of angiogenesis and tumor progression in hematological malignancies

Expression of proteinase-activated receptor 1-4 (PAR 1-4) in human cancer

Thrombin—unique coagulation system protein with multifaceted impacts on cancer and metastasis

Contact Info

Product

Resources

About