FIGURE 1.

Schematic diagram of stroma formation in tumors and wounds. Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) initiates the wound healing response by increasing vascular permeability. As a result, whole plasma including plasma proteins extravasate by way of transcellular (VVO) and/or paracellular pathways. Tumor, connective tissue, and wound cells express tissue factor to trigger the extrinsic clotting system, generating serum, and depositing fibrin. Fibrin provides support for tumor cells and the ingrowth of new blood vessels and fibroblasts that synthesize collagen and other structural proteins. Fibrin degradation products are proangiogenic. Serum reprograms the gene expression patterns of tumor and host connective tissue cells. Over time, vascular connective tissue is replaced by dense fibrous connective tissue stroma termed scar in wounds and desmoplasia in tumors. Modified from Dvorak (2019, Figure 3) and Dvorak (b, Figure 1) with permissions.