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

12 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

Fingerprint

Syndecan-2
Colonic Neoplasms
Neoplasm Metastasis
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Oncology

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

Shed syndecan-2 enhances tumorigenic activities of colon cancer cells. / Choi, Sojoong; Choi, Youngsil; Jun, Eunsung; Kim, In-San; Kim, Seong Eun; Jung, Sung Ae; Oh, Eok Soo.

In: Oncotarget, Vol. 6, No. 6, 01.01.2015, p. 3874-3886.

Research output: Contribution to journalArticle

Choi, S, Choi, Y, Jun, E, Kim, I-S, Kim, SE, Jung, SA & Oh, ES 2015, 'Shed syndecan-2 enhances tumorigenic activities of colon cancer cells', Oncotarget, vol. 6, no. 6, pp. 3874-3886. https://doi.org/10.18632/oncotarget.2885
Choi, Sojoong ; Choi, Youngsil ; Jun, Eunsung ; Kim, In-San ; Kim, Seong Eun ; Jung, Sung Ae ; Oh, Eok Soo. / Shed syndecan-2 enhances tumorigenic activities of colon cancer cells. In: Oncotarget. 2015 ; Vol. 6, No. 6. pp. 3874-3886.
@article{1b068349129a43edb24c1426f34dc54c,
title = "Shed syndecan-2 enhances tumorigenic activities of colon cancer cells",
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.",
keywords = "Colon cancer, Shedding, Signal transduction, Syndecan-2, Tumorigenesis",
author = "Sojoong Choi and Youngsil Choi and Eunsung Jun and In-San Kim and Kim, {Seong Eun} and Jung, {Sung Ae} and Oh, {Eok Soo}",
year = "2015",
month = "1",
day = "1",
doi = "10.18632/oncotarget.2885",
language = "English",
volume = "6",
pages = "3874--3886",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "6",

}

TY - JOUR

T1 - Shed syndecan-2 enhances tumorigenic activities of colon cancer cells

AU - Choi, Sojoong

AU - Choi, Youngsil

AU - Jun, Eunsung

AU - Kim, In-San

AU - Kim, Seong Eun

AU - Jung, Sung Ae

AU - Oh, Eok Soo

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

KW - Colon cancer

KW - Shedding

KW - Signal transduction

KW - Syndecan-2

KW - Tumorigenesis

UR - http://www.scopus.com/inward/record.url?scp=84924228061&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84924228061&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.2885

DO - 10.18632/oncotarget.2885

M3 - Article

C2 - 25686828

AN - SCOPUS:84924228061

VL - 6

SP - 3874

EP - 3886

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 6

ER -