title: Syndecan-1 enhances proliferation, migration and metastasis of HT-1080 cells in cooperation with syndecan-2.
abstract: Syndecans are transmembrane heparan sulphate proteoglycans. Their role in the development of the malignant phenotype is ambiguous and depends upon the particular type of cancer. Nevertheless, syndecans are promising targets in cancer therapy, and it is important to elucidate the mechanisms controlling their various cellular effects. According to earlier studies, both syndecan-1 and syndecan-2 promote malignancy of HT-1080 human fibrosarcoma cells, by increasing the proliferation rate and the metastatic potential and migratory ability, respectively. To better understand their tumour promoter role in this cell line, syndecan expression levels were modulated in HT-1080 cells and the growth rate, chemotaxis and invasion capacity were studied. For in vivo testing, syndecan-1 overexpressing cells were also inoculated into mice. Overexpression of full length or truncated syndecan-1 lacking the entire ectodomain but containing the four juxtamembrane amino acids promoted proliferation and chemotaxis. These effects were accompanied by a marked increase in syndecan-2 protein expression. The pro-migratory and pro-proliferative effects of truncated syndecan-1 were not observable when syndecan-2 was silenced. Antisense silencing of syndecan-2, but not that of syndecan-1, inhibited cell migration. In vivo, both full length and truncated syndecan-1 increased tumour growth and metastatic rate. Based on our in vitro results, we conclude that the tumour promoter role of syndecan-1 observed in HT-1080 cells is independent of its ectodomain; however, in vivo the presence of the ectodomain further increases tumour proliferation. The enhanced migratory ability induced by syndecan-1 overexpression is mediated by syndecan-2. Overexpression of syndecan-1 also leads to activation of IGF1R and increased expression of Ets-1. These changes were not evident when syndecan-2 was overexpressed. These findings suggest the involvement of IGF1R and Ets-1 in the induction of syndecan-2 synthesis and stimulation of proliferation by syndecan-1. This is the first report demonstrating that syndecan-1 enhances malignancy of a mesenchymal tumour cell line, via induction of syndecan-2 expression.
authors: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
authors: Bálint
authors: B
authors: Péterfia
authors: Tibor
authors: T
authors: Füle
authors: Kornélia
authors: K
authors: Baghy
authors: Krisztina
authors: K
authors: Szabadkai
authors: Alexandra
authors: A
authors: Fullár
authors: Katalin
authors: K
authors: Dobos
authors: Fang
authors: F
authors: Zong
authors: Katalin
authors: K
authors: Dobra
authors: Péter
authors: P
authors: Hollósi
authors: András
authors: A
authors: Jeney
authors: Sándor
authors: S
authors: Paku
authors: Ilona
authors: I
authors: Kovalszky
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D006801:Humans; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D053668:Syndecan-1 / Q000235:genetics / Q000378:metabolism*; D053669:Syndecan-2 / Q000235:genetics / Q000378:metabolism*
chemical_list: C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D053668:Syndecan-1; D053669:Syndecan-2; D017526:Receptor, IGF Type 1