[Proteoglycans and breast cancer].
Proteoglycans (PG) are complex sulphated macromolecules composed of linear polysaccharide chains of glycosaminoglycans (GAG) covalently attached to a core protein. These GAG chains contain sulphate groups at various positions, giving them a high density of negative charges, and allowing them to interact with extracellular matrix molecules, including various growth factors. In the developing mammary gland, sulphated proteoglycans participate in morphogenesis and interact with extracellular matrix components in order to constitute a functional matrix. In breast pathogenesis, qualitative or quantitative changes in PG may have important consequences on cell proliferation and/or differentiation. Thus, several studies showed large variations in the nature and distribution of PG/GAG in breast cancer. Accumulation of chondroitin sulfate proteoglycans was described in the stromal compartment of mammary biopsy sections, and content in heparan sulfate proteoglycans, which were more specifically distributed in the epithelial compartment, increased with the level of malignancy and invasiveness of breast cancer tissues. Furthermore, heparan sulfate proteoglycans seem to be involved in control of the growth-promoting activity of numerous growth factors such as fibroblast growth factors also named Heparin-Binding Growth Factors (HBGF). The implication of PG in growth factor activity suggest that PG may have prognostic value in breast cancer. In future, structural studies into the specific HS-sequences involvement in growth factors binding could allow the development of new antiproliferative strategies.
Delehedde
M
M
Unité de Dynamique des Cellules Embryonnaires et Cancéreuses, Centre de Biologie Cellulaire, Université des Sciences et Technologies de Lille, VILLENEUVE-D'ASCO.
Deudon
E
E
Boilly
B
B
Hondermarck
H
H
D001943:Breast Neoplasms / Q000378:metabolism*; D002455:Cell Division; D004847:Epithelial Cells; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D011509:Proteoglycans / Q000737:chemistry / Q000145:classification / Q000378:metabolism*
D006025:Glycosaminoglycans; D011509:Proteoglycans; D005346:Fibroblast Growth Factors