Effects of Glycosaminoglycans on Cell Proliferation of Normal Osteoblasts and Human Osteosarcoma Cells Depend on their Type and Fine Chemical Compositions

• Published in: Anticancer research Vol. 25; no. 4; pp. 2851 - 2856
• Main Authors: NIKITOVIC, D, ZAFIROPOULOS, A, TZANAKAKIS, G. N, KARAMANOS, N. K, TSATSAKIS, A. M
• Format: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01-07-2005
• Subjects: Biological and medical sciences; Bone Neoplasms - chemistry; Bone Neoplasms - drug therapy; Bone Neoplasms - metabolism; Bone Neoplasms - pathology; Cell Growth Processes - drug effects; Cell Line, Transformed; Cell Line, Tumor; Chondroitin Sulfates - pharmacology; Dermatan Sulfate - pharmacology; Diseases of the osteoarticular system; Glycosaminoglycans - isolation & purification; Glycosaminoglycans - metabolism; Glycosaminoglycans - pharmacology; Heparin - pharmacology; Humans; Medical sciences; Osteoblasts - chemistry; Osteoblasts - cytology; Osteoblasts - drug effects; Osteoblasts - metabolism; Osteosarcoma - chemistry; Osteosarcoma - drug therapy; Osteosarcoma - metabolism; Osteosarcoma - pathology; Tumors; Tumors of striated muscle and skeleton; Human; Cell proliferation; glycosaminoglycans; Sarcoma; Diseases of the osteoarticular system; Malignant tumor; Osteoarticular system; Cancerology; Osteosarcoma; Osteoblast; Glycosaminoglycan; Chemical composition; Bone
• ISSN: 0250-7005; 1791-7530

Osteoblastic cells produce a complex extracellular matrix (ECM) composed of a mixture of proteoglycans (PGs), collagens and
non-collagenous proteins. The interaction of proteoglycans with matrix effector macromolecules via either their glycosaminoglycan
(GAG) chains or their protein core is critical in regulating a variety of cellular events. Alterations in the structural composition
of the GAG/PG component of the ECM may have important consequences on cell proliferation and / or differentiation. Human osteoblasts
and two osteosarcoma cell lines, able to produce galactosaminoglycan (GalAGs) and heparan sulphate (HS)-containing proteoglycans,
were treated with their main GAG chain types, and the effects on cell growth were examined. Chondroitin sulphate (CSA) and
dermatan sulphate (DS) inhibited cell proliferation of all osteoblastic cell lines at high concentration (100 μg/ml). DS showed
the stronger inhibitory effect, probably due to the presence of flexible IdoA residues that provide a greater variety in conformation
to these macromolecules. Heparin strongly inhibited the proliferation rates of both normal osteoblasts and transformed osteoblastic
cells at concentrations ≥1 μg/ml. The presence of large amounts of IdoA-derived trisulphated disaccharides, responsible for
the overall negative charge of heparin, should be considered as a critical factor for the inhibition of cell proliferation.
The obtained results suggest that matrix GAGs are factors which affect cell growth of both malignant and normal cells of the
osteoblastic lineage in a concentration-dependent manner. This effect is closely related to the fine chemical structure of
GAGs, i.e. the presence of L-iduronic acid and the degree of sulphation.