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Activation of coagulation and angiogenesis in cancer - immunohistochemical localization in situ of clotting proteins and vascular endothelial growth factor in human cancer

Academic Article
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Overview

authors

  • Shoji, M.
  • Hancock, W. W.
  • Abe, K.
  • Micko, C.
  • Casper, K. A.
  • Baine, R. M.
  • Wilcox, J. N.
  • Danave, I.
  • Dillehay, D. L.
  • Matthews, E.
  • Contrino, J.
  • Morrissey, J. H.
  • Gordon, S.
  • Edgington, Thomas
  • Kudryk, B.
  • Kreutzer, D. L.
  • Rickles, F. R.

publication date

  • February 1998

journal

  • American Journal of Pathology  Journal

abstract

  • Thrombin-catalyzed, cross-linked fibrin (XLF) formation is a characteristic histopathological finding in many human and experimental tumors and is thought to be of importance in the local host defense response. Although the pathogenesis of tumor-associated fibrin deposition is not entirely clear, several tumor procoagulants have been described as likely primary stimuli for the generation of thrombin (and XLF) in the tumor microenvironment (TME). In a previous study of a variety of human tumors we have shown that tissue factor (TF) is the major procoagulant. However, the relative contribution to fibrin deposition in the TME of tumor cell TF and host cell TF (eg, macrophage-derived) was not established. In addition, recent evidence has implicated TF in the regulation of the synthesis of the pro-angiogenic factor vascular endothelial growth factor (VEGF) by tumor cells. In the current study we used in situ techniques to determine the cellular localization of XLF, TF, VEGF, and an alternative tumor procoagulant, so-called cancer procoagulant (CP), a cysteine protease that activates clotting factor X. In lung cancer we have found XLF localized predominantly to the surface of tumor-associated macrophages, as well as to some endothelial cells and perivascular fibroblasts in the stromal area of the tumors co-distributed with TF at the interface of the tumor and host cells. Cancer pro-coagulant was localized to tumor cells in several cases but not in conjunction with the deposition of XLF. TF and VEGF were co-localized in both lung cancer and breast cancer cells by in situ hybridization and immunohistochemical staining. Furthermore, a strong relationship was found between the synthesis of TF and VEGF levels in human breast cancer cell lines (r2 = 0.84; P < 0.0001). Taken together, these data are consistent with a highly complex interaction between tumor cells, macrophages, and endothelial cells in the TME leading to fibrin formation and tumor angiogenesis.

subject areas

  • Blood Coagulation
  • Blood Coagulation Factors
  • Breast Neoplasms
  • Endothelial Growth Factors
  • Female
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms
  • Lymphokines
  • Neovascularization, Pathologic
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
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Identity

PubMed Central ID

  • PMC1857968

International Standard Serial Number (ISSN)

  • 0002-9440

PubMed ID

  • 9466566
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Additional Document Info

start page

  • 399

end page

  • 411

volume

  • 152

issue

  • 2

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