Shed syndecan-2 enhances tumorigenic activities of colon cancer cells
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Sojoong Choi1,2, Youngsil Choi1, Eunsung Jun2, In-San Kim2,3, Seong-Eun Kim4, Sung-Ae Jung4, Eok-Soo Oh1
1Department of Life Sciences and the Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 120–750, Republic of Korea
2Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seongbuk-gu, Seoul 136–791, Korea
3Department of Biochemistry and Cell Biology, School of Medicine and Cell & Matrix Research Institute, Kyungpook National University, Daegu 700–422, Republic of Korea
4Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul 158–710, Republic of Korea
Eok-Soo Oh, e-mail: [email protected]
Keywords: Colon cancer, shedding, signal transduction, syndecan-2, tumorigenesis
Received: November 03, 2014 Accepted: December 09, 2014 Published: February 17, 2015
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 Asn148-Leu149 residues were replaced with Asn148-Ile149, 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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