Effect of syndecan-1 overexpression on mesenchymal tumour cell proliferation with focus on different functional domains

Syndecan-1 过表达对间充质肿瘤细胞增殖的影响(重点关注不同功能域)

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作者:F Zong, E Fthenou, J Castro, B Péterfia, I Kovalszky, L Szilák, G Tzanakakis, K Dobra

Conclusions

Both full-length and truncated syndecan-1 inhibited proliferation of the mesenchymal tumour cells, providing new insights into the importance for cancer growth of different functional domains of this proteoglycan.

Methods

We transfected cells of two mesenchymal tumour cell lines with a full-length syndecan-1 construct and three truncated variants, namely 78 construct lacking the EC domain with exception of DRKE sequence; 77 construct lacking extracellular the whole domain and RMKKK corresponding to a short cytoplasmic motif. Subcellular distribution was revealed using confocal laser microscopy. Overexpression of the constructs was verified using real-time RT-PCR and by FACS analysis and effects of syndecan-1 on cell behaviour were explored. Cell cycle analysis allowed for dissection of mechanisms regulating cell proliferation.

Results

Overexpression of syndecan-1 influenced expression profile of the other syndecan members, and decreased tumour cell proliferation significantly by two mechanisms, as follows: increased length of G0/G1 phase was the most evident change in RMKKK and 77 transfectants, whereas prolonged S phase was more obvious in full-length transfectants. Overexpression of syndecan-1 changed the tumour cell morphology in an epithelioid direction. Conclusions: Both full-length and truncated syndecan-1 inhibited proliferation of the mesenchymal tumour cells, providing new insights into the importance for cancer growth of different functional domains of this proteoglycan.

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