Choi, Sojoong Choi, Youngsil Jun, Eunsung Kim, In-San Kim, Seong-Eun Jung, Sung-Ae Oh, Eok-Soo 2024-01-20T07:33:55Z 2024-01-20T07:33:55Z 2021-09-05 2015-02-28 1949-2553 https://pubs.kist.re.kr/handle/201004/125748 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. English IMPACT JOURNALS LLC HEPARAN-SULFATE PROTEOGLYCANS COLORECTAL-CANCER MULTIPLE-MYELOMA CARCINOMA CELLS DISEASE EXPRESSION HEALTH ROLES MIGRATION ADHESION Shed syndecan-2 enhances tumorigenic activities of colon cancer cells Article 10.18632/oncotarget.2885 1 ONCOTARGET, v.6, no.6, pp.3874 - 3886 ONCOTARGET 6 6 3874 3886 scie scopus 000352696200035 2-s2.0-84924228061 Oncology Cell Biology Oncology Cell Biology Article HEPARAN-SULFATE PROTEOGLYCANS COLORECTAL-CANCER MULTIPLE-MYELOMA CARCINOMA CELLS DISEASE EXPRESSION HEALTH ROLES MIGRATION ADHESION Colon cancer shedding signal transduction syndecan-2 tumorigenesis