Shed syndecan-2 enhances tumorigenic activities of colon cancer cells

Sojoong Choi, Youngsil Choi, Eunsung Jun, In-San Kim, Seong Eun Kim, Sung Ae Jung, Eok Soo Oh

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 Asn148- Leu149 residues were replaced with Asn148-Ile149, had decreased shedding, less cancerassociated 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 cancerconditioned 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.

Original languageEnglish
Pages (from-to)3874-3886
Number of pages13
JournalOncotarget
Volume6
Issue number6
DOIs
Publication statusPublished - 2015 Jan 1
Externally publishedYes

Keywords

  • Colon cancer
  • Shedding
  • Signal transduction
  • Syndecan-2
  • Tumorigenesis

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'Shed syndecan-2 enhances tumorigenic activities of colon cancer cells'. Together they form a unique fingerprint.

  • Cite this

    Choi, S., Choi, Y., Jun, E., Kim, I-S., Kim, S. E., Jung, S. A., & Oh, E. S. (2015). Shed syndecan-2 enhances tumorigenic activities of colon cancer cells. Oncotarget, 6(6), 3874-3886. https://doi.org/10.18632/oncotarget.2885