Ovarian cancer, the coagulation pathway, and inflammation

Xipeng Wang, Ena Wang, John J. Kavanagh, Ralph S. Freedman

Research output: Contribution to journalReview article

86 Citations (Scopus)

Abstract

Epithelial ovarian cancer (EOC) represents the most frequent cause of death in the United States from a cancer involving the female genital tract. Contributing to the overall poor outcome in EOC patients, are the metastases to the peritoneum and stroma that are common in this cancer. In one study, cDNA microarray analysis was performed on fresh tissue to profile gene expression in patients with EOC. This study showed a number of genes with significantly altered expression in the pelvic peritoneum and stroma, and in the vicinity of EOC implants. These genes included those encoding coagulation factors and regulatory proteins in the coagulation cascade and genes encoding proteins associated with inflammatory responses. In addition to promoting the formation of blood clots, coagulation factors exhibit many other biologic functions as well as tumorigenic functions, the later including tumor cell proliferation, angiogenesis, invasion, and metastasis. Coagulation pathway proteins involved in tumorigenesis consist of factor II (thrombin), thrombin receptor (protease-activated receptors), factor III (tissue factor), factor VII, factor X and factor I (fibrinogen), and fibrin and factor XIII. In a recent study we conducted, we found that factor XII, factor XI, and several coagulation regulatory proteins, including heparin cofactor-II and epithelial protein C receptor (EPCR), were also upregulated in the peritoneum of EOC. In this review, we summarize evidence in support of a role for these factors in promoting tumor cell progression and the formation of ascites. We also discuss the different roles of coagulation factor pathways in the tumor and peritumoral microenvironments as they relate to angiogenesis, proliferation, invasion, and metastasis. Since inflammatory responses are another characteristic of the peritoneum in EOC, we also discuss the linkage between the coagulation cascade and the cytokines/chemokines involved in inflammation. Interleukin-8, which is considered an important chemokine associated with tumor progression, appears to be a linkage point for coagulation and inflammation in malignancy. Lastly, we review findings regarding the inflammatory process yielded by certain clinical trials of agents that target members of the coagulation cascade in the treatment of cancer. Current data suggest that disrupting certain elements of the coagulation and inflammation processes in the tumor microenvironment could be a new biologic approach to cancer therapeutics.

Original languageEnglish
Article number25
JournalJournal of Translational Medicine
Volume3
DOIs
Publication statusPublished - 21 Jun 2005
Externally publishedYes

Fingerprint

Coagulation
Ovarian Neoplasms
Tumors
Inflammation
Blood Coagulation Factors
Peritoneum
Neoplasms
Thromboplastin
Chemokines
Fibrinogen
Tumor Microenvironment
Proteins
Neoplasm Metastasis
Genes
Heparin Cofactor II
Proteinase-Activated Receptors
Factor XI
Factor XII
Thrombin Receptors
Factor XIII

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Ovarian cancer, the coagulation pathway, and inflammation. / Wang, Xipeng; Wang, Ena; Kavanagh, John J.; Freedman, Ralph S.

In: Journal of Translational Medicine, Vol. 3, 25, 21.06.2005.

Research output: Contribution to journalReview article

Wang, Xipeng ; Wang, Ena ; Kavanagh, John J. ; Freedman, Ralph S. / Ovarian cancer, the coagulation pathway, and inflammation. In: Journal of Translational Medicine. 2005 ; Vol. 3.
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