Proteoglycans: Master modulators of paracrine fibroblast-carcinoma cell interactions

Reciprocal interactions between tumor and stromal cells govern carcinoma growth and progression. Signaling functions between these cell types in the tumor microenvironment are largely carried out by secreted growth factors and cytokines. This review discusses how proteoglycans, which are abundantly present in normal and neoplastic tissues, modulate paracrine growth factor signaling events. General principles of proteoglycan involvement in paracrine signaling include stromal induction, core protein processing by proteases and growth factor binding via proteoglycan glycosaminoglycan chains or core protein domains.