Figure 2.

CCN4 as an autocrine and paracrine mediator within the tumor microenvironment.

Notes: CCN4 is produced and secreted (blue arrows) by tumor cells as well as by stromal fibroblasts. Secreted CCN4 is then available to exert effects (red arrows) on tumor cells and vascular endothelial cells through both paracrine and autocrine mechanisms. CCN4 is able to bind to extracellular matrix proteins (eg, fibronectin; green shapes), as well as to integrins (blue shapes) in the cell membrane, thereby modulating cell interactions with the extracellular matrix. Integrins are expressed by all of the cell types depicted.