Syndecan-1 enhances proliferation, migration and metastasis of HT-1080 cells in cooperation with Syndecan-2

Bálint Péterfia, T. Füle, Kornélia Baghy, Krisztina Szabadkai, Alexandra Fullár, Katalin Dobos, Fang Zong, Katalin Dobra, Péter Hollósi, A. Jeney, S. Paku, I. Kovalszky

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish
Article numbere39474
JournalPLoS One
Volume7
Issue number6
DOIs
Publication statusPublished - Jun 26 2012

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Syndecan-2
Syndecan-1
metastasis
Neoplasm Metastasis
neoplasms
Syndecans
chemotaxis
cells
promoter regions
cell lines
Tumors
Neoplasms
Aptitude
fibrosarcoma
Chemotaxis
proteoglycans
Carcinogens
cell movement
Cells
protein synthesis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Syndecan-1 enhances proliferation, migration and metastasis of HT-1080 cells in cooperation with Syndecan-2. / Péterfia, Bálint; Füle, T.; Baghy, Kornélia; Szabadkai, Krisztina; Fullár, Alexandra; Dobos, Katalin; Zong, Fang; Dobra, Katalin; Hollósi, Péter; Jeney, A.; Paku, S.; Kovalszky, I.

In: PLoS One, Vol. 7, No. 6, e39474, 26.06.2012.

Research output: Contribution to journalArticle

Péterfia, Bálint ; Füle, T. ; Baghy, Kornélia ; Szabadkai, Krisztina ; Fullár, Alexandra ; Dobos, Katalin ; Zong, Fang ; Dobra, Katalin ; Hollósi, Péter ; Jeney, A. ; Paku, S. ; Kovalszky, I. / Syndecan-1 enhances proliferation, migration and metastasis of HT-1080 cells in cooperation with Syndecan-2. In: PLoS One. 2012 ; Vol. 7, No. 6.
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AU - Fullár, Alexandra

AU - Dobos, Katalin

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AU - Dobra, Katalin

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