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Am J Physiol Cell Physiol 296: C505-C513, 2009. First published December 31, 2008; doi:10.1152/ajpcell.00472.2008
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EXTRACELLULAR MATRIX, CELL INTERACTIONS

Podocalyxin-like protein is an E-/L-selectin ligand on colon carcinoma cells: comparative biochemical properties of selectin ligands in host and tumor cells

Susan N. Thomas,1 Ronald L. Schnaar,2 and Konstantinos Konstantopoulos1

Department of 1Chemical and Biomolecular Engineering and 2Pharmacology and Neuroscience, The Johns Hopkins University, Baltimore, Maryland

Submitted 13 September 2008 ; accepted in final form 25 December 2008

Selectins facilitate metastasis and tumor cell arrest in the microvasculature by mediating binding of selectin-expressing host cells to ligands on tumor cells. We recently identified CD44 variant isoforms as functional P-, but not E-/L-, selectin ligands on colon carcinoma cells. Furthermore, a ~180-kDa sialofucosylated glycoprotein(s) mediated selectin binding in CD44-knockdown cells. Using immunoaffinity chromatography and tandem mass spectrometry, we identify podocalyxin-like protein (PCLP) as an alternative selectin ligand. Blot rolling and cell-free flow-based adhesion assays disclose that PCLP on LS174T colon carcinoma cells possesses E-/L-, but not P-, selectin binding activity. The selectin-binding determinants on LS174T PCLP are non-MECA-79-reactive sialofucosylated structures displayed on O-linked glycans, distinct from the MECA-79-reactive O-glycans on PCLP expressed by high endothelial venules, which is an L-selectin ligand. PCLP on CD44-knockdown LS174T cells exhibits higher HECA-452 immunoreactivity than PCLP on wild-type cells, suggesting that PCLP functions as an alternative acceptor for selectin-binding glycans. The enhanced expression of HECA-452 reactivity on PCLP from CD44-knockdown cells correlates with the increased avidity of PCLP for E- but not L-selectin. The novel finding that PCLP is an E-/L-selectin ligand on carcinoma cells offers a unifying perspective on the apparent enhanced metastatic potential associated with tumor cell PCLP overexpression and the role of selectins in metastasis.

adhesion; metastasis; colon carcinoma cells; fluid shear


Address for reprint requests and other correspondence: K. Konstantopoulos, Dept. of Chemical and Biomolecular Engineering, The Johns Hopkins Univ., 3400 N. Charles St., Baltimore, MD 21218 (e-mail: kkonsta1{at}jhu.edu)






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