Mucin 16 is a functional selectin ligand on pancreatic cancer cells

Shih Hsun Chen, Matthew R. Dallas, Eric M. Balzer, Konstantinos Konstantopoulos

Research output: Contribution to journalArticle

Abstract

Selectins promote metastasis by mediating specific interactions between selectin ligands on tumor cells and selectin-expressing host cells in the microvasculature. Using affinity chromatography in conjunction with tandem mass spectrometry and bioinformatics tools, we identified mucin 16 (MUC16) as a novel selectin ligand expressed by metastatic pancreatic cancer cells. While up-regulated in many pancreatic cancers, the biological function of sialofucosylated MUC16 has yet to be fully elucidated. To address this, we employed blot rolling and cell-free flow-based adhesion assays using MUC16 immunopurified from pancreatic cancer cells and found that it efficiently binds E- and L- but not P-selectin. The selectin-binding determinants are sialofucosylated structures displayed on Oand N-linked glycans. Silencing MUC16 expression by RNAi markedly reduces pancreatic cancer cell binding to E- and L-selectin under flow. These findings provide a novel integrated perspective on the enhanced metastatic potential associated with MUC16 overexpression and the role of selectins in metastasis.

Original languageEnglish (US)
Pages (from-to)1349-1359
Number of pages11
JournalFASEB Journal
Volume26
Issue number3
DOIs
StatePublished - Mar 1 2012

Keywords

  • MUC16
  • Metastasis
  • Shear stress

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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