Delehedde M, Deudon E, Boilly B, Hondermarck H
Unité de Dynamique des Cellules Embryonnaires et Cancéreuses, Centre de Biologie Cellulaire, Université des Sciences et Technologies de Lille, VILLENEUVE-D'ASCO.
Pathol Biol (Paris). 1997 Apr;45(4):305-11.
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.
蛋白聚糖(PG)是由共价连接到核心蛋白的糖胺聚糖(GAG)线性多糖链组成的复杂硫酸化大分子。这些GAG链在不同位置含有硫酸基团,赋予它们高密度的负电荷,并使其能够与细胞外基质分子相互作用,包括各种生长因子。在发育中的乳腺中,硫酸化蛋白聚糖参与形态发生并与细胞外基质成分相互作用,以构成功能性基质。在乳腺发病机制中,PG的定性或定量变化可能对细胞增殖和/或分化产生重要影响。因此,多项研究表明乳腺癌中PG/GAG的性质和分布存在很大差异。在乳腺活检切片的基质部分描述了硫酸软骨素蛋白聚糖的积累,而硫酸乙酰肝素蛋白聚糖的含量在恶性和侵袭性乳腺癌组织中随水平升高而增加,其更特异性地分布在上皮部分。此外,硫酸乙酰肝素蛋白聚糖似乎参与了对多种生长因子如成纤维细胞生长因子(也称为肝素结合生长因子,HBGF)的促生长活性的控制。PG对生长因子活性的影响表明PG可能在乳腺癌中具有预后价值。未来,对参与生长因子结合的特定HS序列的结构研究可能会促成新的抗增殖策略的开发。