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Cited by 36Blood Coagulation and Thrombosis MechanismsVenous Thromboembolism Diagnosis and ManagementSarcoma Diagnosis and Treatment

Thrombin induces osteosarcoma growth, a function inhibited by low molecular weight heparin in vitro and in vivo: Procoagulant nature of osteosarcoma

Ichikawa, Jiro, Cole, Heather A., Magnussen, Robert A., Mignemi, Nicholas A., Butler, Matthew, Holt, Ginger E., O'Rear, Lynda, Yuasa, Masato +6 more·2012·Cancer
DOI 10.1002/cncr.26518
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Abstract

BACKGROUND: Procoagulant states, leading to activation of the coagulation protease thrombin, are common in cancer and portend a poor clinical outcome. Although procoagulant states in osteosarcoma patients have been described, studies exploring osteosarcoma cells' ability to directly contribute to procoagulant activity have not been reported. This study explores the hypothesis that osteosarcoma can regulate thrombin generation and proliferate in response to thrombin, and that attenuating thrombin generation with anticoagulants can slow tumor growth. METHODS: Pathologic analysis of osteosarcoma with adjacent venous thrombus was performed. In vitro proliferation assays, cell‐based coagulant activity assays, and quantification of coagulation cofactor expression were performed on human and murine osteosarcoma cell lines with varying aggressiveness. The efficacy of low molecular weight heparin (LMWH) attenuation of tumor‐dependent thrombin generation and growth in vitro and in vivo was determined. RESULTS: Venous thrombi adjacent to osteosarcoma were found to harbor tumor surrounded by fibrin expressing coagulation cofactors, a finding associated with poor clinical outcome. More aggressive osteosarcoma cell lines had greater surface expression of procoagulant factors and generated more thrombin than less aggressive cell lines and were found to proliferate in response to thrombin. Treatment with LMWH reduced in vitro osteosarcoma proliferation and procoagulant activity as well as tumor growth in vivo. CONCLUSIONS: These findings suggest that elements of the coagulation cascade may play a role in and represent a pharmaceutical target to disrupt osteosarcoma growth. They also have broader implications, as they suggest that, to be effective, dosing of anticoagulants must take into account an individual tumor's capacity to generate thrombin. Cancer 2012. © 2011 American Cancer Society.

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  • Triggering the haemostatic cascade is important for the early survival of disseminated osteosarcoma cells.

    “Evidence further suggests that triggering the haemostatic cascade is important for the early survival of disseminated cells 75,76 .”

    From Osteosarcoma (2022) · cites this paper as [76]

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Authors
Ichikawa, J., Cole, H. A., Magnussen, R. A., Mignemi, N. A., Butler, M., Holt, G. E., O'Rear, L., Yuasa, M., Pabla, B., Haro, H., Cates, J. M. M., Hamm, H. E., Schwartz, H. S., & Schoenecker, J. G.
Affiliations
  • University of Yamanashi (JP)
  • Vanderbilt University Medical Center (US)
Corresponding author
Schoenecker, Jonathan G.
ORCID
Venue
Cancer
Publisher
Wiley
Published
2011-09-27
Volume
118
Issue
9
Pages
2494-2506
ISSN
  • 0008-543X (ISSN-L)
  • 1097-0142
DOI
10.1002/cncr.26518
OpenAlex
W1588736822
Cited by
36
References
36
Citations by year
2026: 2 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 2 · 2019: 7 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 6 · 2013: 1 · 2012: 3
FWCI
2.19
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Cancer (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
  • Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
Keywords
osteosarcoma, thrombin, low molecular weight heparin, procoagulant activity, tumor growth, coagulation cascade, venous thrombus, fibrin, coagulation cofactors, anticoagulation, tumor aggressiveness
MeSH terms
Adolescent, Adult, Animals, Blood Coagulation, Bone Neoplasms, Female, Heparin, Humans, Male, Middle Aged, Osteosarcoma, Thrombin, Venous Thrombosis, Cell Line, Tumor, Cell Proliferation, Mice, Young Adult

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