Glycosaminoglycans and activated contact system in cancer patient plasmas

Jing Pan, Yi Qian, Peter Weiser, Xiaodong Zhou, Hong Lu, Daniel R. Studelska, Lijuan Zhang

Research output: Chapter in Book/Report/Conference proceedingChapter

18 Scopus citations

Abstract

Oncogenic mutations create cancer cells. Cancer cells require thrombin for growth, angiogenesis, and metastasis. All cancer patients display a hypercoagulable state, which includes platelet activation, blood coagulation, complement activation, vasodilatation, and inflammation. This often results in thrombosis, the second leading cause of death in cancer patients. It is established that chemically oversulfated glycosaminoglycans (GAGs) induce thrombin generation through contact system activation in human plasma. Thrombin is responsible for thrombosis. In this chapter, we show that plasmas from lung cancer patients contain activated contact systems apparent by the absence of high molecular weight kininogen and processed C1inh, by abnormal kallikrein and thrombin activities, and by increased glucosamine, galactosamine, and GAG levels. Activated contact systems were also evident in plasmas from breast, colon, and pancreatic cancer patients. These data suggest that GAGs or other molecules produced by tumors induce abnormal thrombin generation through contact system activation. Therefore, the contact system and glycans represent new targets for cancer diagnosis, prevention, and treatment.

Original languageEnglish (US)
Title of host publicationProgress in Molecular Biology and Translational Science
PublisherElsevier B.V.
Pages473-495
Number of pages23
EditionC
DOIs
StatePublished - 2010

Publication series

NameProgress in Molecular Biology and Translational Science
NumberC
Volume93
ISSN (Print)1877-1173

Keywords

  • C1 inhibitor
  • Cancer
  • Factor XII
  • Glycosaminoglycan
  • Kallikrein
  • Kininogen
  • TAFI
  • Thrombin

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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