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Transforming Growth Factor‐β as a key molecule triggering the expression of versican isoforms v0 and v1, Hyaluronan Synthase‐2 and synthesis of Hyaluronan in Malignant Osteosarcoma cells
Author(s) -
Nikitovic D.,
Zafiropoulos A.,
Katonis P.,
Tsatsakis A.,
Theocharis A. D.,
Karamanos N. K.,
Tzanakakis G. N.
Publication year - 2006
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/15216540500531713
Subject(s) - versican , hyaluronan synthase , microbiology and biotechnology , growth factor , chemistry , extracellular matrix , cell growth , hyaluronic acid , autocrine signalling , platelet derived growth factor receptor , proteoglycan , biology , biochemistry , receptor , anatomy
Versican, a large sized chondroitin‐sulphate proteoglycan (PG), and its binding partner, hyaluronan (HA), are extracellular matrix (ECM) components that play an essential role in transformed cell behavior. Expression of certain versican isoforms has been implicated in cell migration and proliferation of cancer cells and, on the other hand, disruption of HA synthesis by inhibiting hyaluronan synthase‐2 (HAS2) expression in osteosarcoma cells by suppressing cell proliferation, invasiveness and motility. Considering that growth factors, such as TGF‐β, bFGF and PDGF‐BB, are important regulators for the expression of the ECM macromolecules, in this study we examined the effect of these growth factors on the expression of the various versican isoforms, HA synthases as well as HA synthesis by MG‐63 osteosarcoma cells and normal human osteoblastic periodontal ligament cells (hPDL). Real‐time PCR and metabolic labelling followed by fine HPLC analysis coupled to radiochemical detection were the methods utilized. It was found that, contrary to normal hPDL cells, osteosarcoma MG‐63 cells do not constitutively express the versican isoforms V0 and V1. Exogenous addition of TGF‐β2 stimulated the versican transcript levels mainly by forcing osteosarcoma cells to express V1 and V0 isoforms. PDGF‐BB and bFGF had only minor effects in these cells. In hPDL cells a strong stimulation of the V3 transcript by all growth factors was observed. TGF‐β2 was also the major stimulator of HAS2 isoform expression as well as hyaluronan synthesis in osteosarcoma cells, while PDGF‐BB exerted dominant influence on HAS2 isoform expression and hyaluronan biosynthesis by osteoblasts. The obtained results show for the first time that TGF‐β2 triggers the malignant phenotype pattern of versican and hyaluronan expression in human osteosarcoma cells and indicate that this growth factor may account for the metastatic potential of these cells.IUBMB Life, 58: 47 ‐ 53, 2006