Proteoglycans: master modulators of paracrine fibroblast-carcinoma cell interactions

Abstract

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.

Figure 1

Aberrant stromal expression of cell surface proteoglycans: A) Strong and diffuse syndecan-1 expression in stromal fibroblasts of a breast carcinoma. B) Glypican-1 expression in stromal fibroblasts of a breast carcinoma.

Figure 2

Schematic representation of the role of stromal syndecan-1 and decorin in normal mammary gland and breast cancer.