Shed syndecan-2 enhances colon cancer progression by increasing cooperative angiogenesis in the tumor microenvironment

Bohee Jang, Hyun Kuk Song, Jisun Hwang, Seohyeon Lee, Eunhye Park, Areum Oh, Eun Sook Hwang, Jee Young Sung, Yong Nyun Kim, Kyunghye Park, You Mie Lee, Eok Soo Oh

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Although shed syndecan-2 potentiated the tumorigenic activities of colon cancer cells, how shed syndecan-2 increases this tumorigenic potential remains unclear. Using an orthotopic mouse model of colon cancer, we show that shed syndecan-2 increases colon cancer progression by cooperatively promoting angiogenesis. Co-administration with a synthetic peptide of shed syndecan-2 (S2LQ) enhanced the survival and tumor engraftment of luciferase-expressing CT26 colon adenocarcinoma cells orthotopically implanted into the cecum of BALB/c mice. Intravenous injection of S2LQ further enhanced the growth of orthotopic tumors in the cecum, with increases in the tissue infiltration of macrophages and the formation of blood vessels, mainly in peripheral layers of the tumor facing the stroma. Furthermore, S2LQ stabilized HIF1α and enhanced the VEGF expression in human colon cancer cell lines, and increased the migration of RAW 264.7 murine macrophage cells and bone marrow-derived macrophages. Finally, S2LQ increased the tube formation of vascular endothelial cells in vitro. Together, these data demonstrate that shed syndecan-2 enhances tumorigenic activity by increasing the crosstalk of cancer cells with tumor-associated macrophages and endothelial cells to enhance angiogenesis for colon cancer progression in the tumor microenvironment.

Original languageEnglish
Pages (from-to)40-58
Number of pages19
JournalMatrix Biology
StatePublished - Mar 2022

Bibliographical note

Funding Information:
This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) ( 2019R1A2C2009011 to ESO, NRF-2018R1D1A1B07049726 to BHJ, and NRF-2020R1A5A2017323 to YML).

Publisher Copyright:
© 2022 The Author(s)


  • Angiogenesis
  • Orthotopic model
  • Syndecan-2
  • Tumor microenvironment


Dive into the research topics of 'Shed syndecan-2 enhances colon cancer progression by increasing cooperative angiogenesis in the tumor microenvironment'. Together they form a unique fingerprint.

Cite this