Fibrin as a component of the tumor stroma: origins and biological significance

Abstract

An association between cancer and the coagulation system was suggested by Trousseau more than a century ago and initial reports of fibrin deposition in the stroma of solid tumors date back some 25 years. However, the validity and generality of these observations have only quite recently been established, and their implications for an understanding of tumor biology, metastasis, and therapy are only now coming to be appreciated by investigators in the mainstream of cancer research. This article reviews the current status of fibrin's role in the biology of tumor growth, considering in turn: (1) the evidence that fibrin is present in tumors, the nature of such fibrin, and its relation to plasma fibronectin; (2) the mechanisms by which fibrin may come to be deposited in tumors; and (3) the potential biological and medical significance of tumorassociated fibrin deposition and degradation. Among the last are such important possibilities as a barrier function to the immune response and possible roles in angiogenesis, desmoplasia, and metastasis.

A general reaction–diffusion model of acidity in cancer invasion

“…9) are at odds with past experimental results that saw no such correlations (Dvorak et al 1983), indicating that something more must be influencing the system dynamics than we have considered here. While the Gatenby-Gawlinski model was an elegant first investigation into the acid-mediated invasion hypothesis, and the generalisation presented in this paper provides a formulation applicable to a wider variety of tumour scenarios, both are coarse-grained descriptions of the tissue-scale dynamics.…”

“…Finally, some past experiments have indicated a lack of correlation between speed of invasion and the density of healthy cells, stroma, and other material mixed in with the tumour (Dvorak et al 1983). Sampling our (a 1 , a 2 , d 1 , d 2 ) parameter space while holding all other parameters constant reveals the presence of a negative correlation Fig.…”

Targeting tissue factor on tumor vascular endothelial cells and tumor cells for immunotherapy in mouse models of prostatic cancer

“…These cells are sequestered from contact with fVII by the tight endothelial cell layer of the normal vasculature (8), preventing blood clots from forming in normal tissues unless the endothelium is damaged. However, blood clots do occur in tumors (9,10), presumably as a result of TF expression on tumor vascular endothelial cells and also on tumor cells that are accessible to fVII because the tumor vascular endothelium is leaky (8,(11)(12)(13)(14). Although blood clots in tumors do not prevent tumor growth and metastasis, otherwise cancer would not be a major cause of death, tumor growth has been inhibited by targeting additional TF molecules to the tumor vascular endothelium to enhance clotting (15).…”

Urokinase Induces Expression of Its Own Receptor in Beas2B Lung Epithelial Cells

“…Extracellular proteolytic enzymes including serine proteinases and metalloproteinases have been implicated in remodeling of the extracellular matrix in lung injury and lung neoplasia (1)(2)(3). These enzymes influence inflammatory cell traffic or cancer cell invasiveness via the breakdown of basement membranes and extracellular matrix (4 -7).…”