Leaky Vessels, Fibrin Deposition, and Fibrosis: A Sequence of Events Common to Solid Tumors and to Many Other Types of Disease

Abstract

Solid tumors must induce new blood vessels if they are to grow beyond minimal size. As an initial step in this process, tumors secrete a vascular permeability factor that renders the local microvasculature hyperpermeable to fibrinogen and to other plasma proteins. Extravasated fibrinogen is rapidly clotted to crosslinked fibrin gel. Over time, this gel is invaded by macrophages, fibroblasts, and endothelial cells and undergoes "organization," such that it is replaced by vascularized granulation tissue and finally by mature connective tissue. This sequence of events is not unique to tumors but occurs in wound-healing and in a wide variety of other disease processes, including some that prominently affect the lung.