α3 Chains of type V collagen regulate breast tumour growth via glypican-1

Pericellular alpha 3(V) collagen can affect the functioning of cells, such as adipocytes and pancreatic beta cells. Here we show that alpha 3(V) chains are an abundant product of normal mammary gland basal cells, and that alpha 3(V) ablation in a mouse mammary tumour model inhibits mammary tumour progression by reducing the proliferative potential of tumour cells. These effects are shown to be primarily cell autonomous, from loss of alpha 3(V) chains normally produced by tumour cells, in which they affect growth by enhancing the ability of cell surface proteoglycan glypican-1 to act as a co-receptor for FGF2. Thus, a mechanism is presented for microenvironmental influence on tumour growth. alpha 3(V) chains are produced in both basal-like and luminal human breast tumours, and its expression levels are tightly coupled with those of glypican-1 across breast cancer types. Evidence indicates alpha 3(V) chains as potential targets for inhibiting tumour growth and as markers of oncogenic transformation.