Serglycin is a
proteoglycan expressed by some malignant cells. It promotes
metastasis and protects some
tumor cells from
complement system attack. In the present study, we show for the first time the in situ expression of
serglycin by
breast cancer cells by immunohistochemistry in patients' material. Moreover, we demonstrate high expression and constitutive secretion of
serglycin in the aggressive MDA-MB-231
breast cancer cell line.
Serglycin exhibited a strong cytoplasmic staining in these cells, observable at the cell periphery in a thread of filaments near the cell membrane, but also in filopodia-like structures.
Serglycin was purified from
conditioned medium of MDA-MB-231 cells, and represented the major
proteoglycan secreted by these cells, having a molecular size of ~ 250 kDa and carrying
chondroitin sulfate side chains, mainly composed of 4-sulfated (~ 87%), 6-sulfated (~ 10%) and non-sulfated (~ 3%)
disaccharides. Purified
serglycin inhibited early steps of both the classical and the
lectin pathways of
complement by binding to C1q and
mannose-binding lectin. Stable expression of
serglycin in less aggressive MCF-7
breast cancer cells induced their proliferation, anchorage-independent growth, migration and invasion. Interestingly, over-expression of
serglycin lacking the
glycosaminoglycan attachment sites failed to promote these cellular functions, suggesting that glycanation of
serglycin is a pre-requisite for its oncogenic properties. Our findings suggest that
serglycin promotes a more aggressive
cancer cell phenotype and may protect
breast cancer cells from
complement attack supporting their survival and expansion.