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

Abstract

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
Volume107
DOIs
StatePublished - Mar 2022

Keywords

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

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