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Shed syndecan-2 enhances tumorigenic activities of colon cancer cells

Title
Shed syndecan-2 enhances tumorigenic activities of colon cancer cells
Authors
Choi, SojoongChoi, YoungsilJun, EunsungKim, In-SanKim, Seong-EunJung, Sung-AeOh, Eok-Soo
Ewha Authors
오억수정성애김성은
SCOPUS Author ID
오억수scopus; 정성애scopus; 김성은scopus
Issue Date
2015
Journal Title
ONCOTARGET
ISSN
1949-2553JCR Link
Citation
vol. 6, no. 6, pp. 3874 - 3886
Keywords
Colon cancersheddingsignal transductionsyndecan-2tumorigenesis
Publisher
IMPACT JOURNALS LLC
Indexed
SCIE; SCOPUS WOS
Abstract
Because earlier studies showed the cell surface heparan sulfate proteoglycan, syndecan-2, sheds from colon cancer cells in culture, the functional roles of shed syndecan-2 were assessed. A non-cleavable mutant of syndecan-2 in which the Asn(148)-Leu(149) residues were replaced with Asn(148)-Ile(149), had decreased shedding, less cancer-associated activities of syndecan-2 in vitro, and less syndecan-2-mediated metastasis of mouse melanoma cells in vivo, suggesting the importance of shedding on syndecan-2-mediated pro-tumorigenic functions. Indeed, shed syndecan-2 from cancer-conditioned media and recombinant shed syndecan-2 enhanced cancer-associated activities, and depletion of shed syndecan-2 abolished these effects. Similarly, shed syndecan-2 was detected from sera of patients from advanced carcinoma (625.9 ng/ml) and promoted cancer-associated activities. Furthermore, a series of syndecan-2 deletion mutants showed that the tumorigenic activity of shed syndecan-2 resided in the C-terminus of the extracellular domain and a shed syndecan-2 synthetic peptide (16 residues) was sufficient to establish subcutaneous primary growth of HT29 colon cancer cells, pulmonary metastases (B16F10 cells), and primary intrasplenic tumor growth and liver metastases (4T1 cells). Taken together, these results demonstrate that shed syndecan-2 directly enhances colon cancer progression and may be a promising therapeutic target for controlling colon cancer development.
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