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PMID: 10433939 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Distinct selectin ligands on colon carcinoma mucins can mediate pathological interactions among platelets, leukocytes, and endothelium.

The American journal of pathology ·Vol. 155 ·No. 2 ·1999-08-00 ·Pages 461-72

Kim YJ, Borsig L, Han HL, Varki NM, Varki A

Abstract

Selectins are adhesion molecules that mediate calcium-dependent cell-cell interactions among leukocytes, platelets, and endothelial cells. The naturally occurring vascular ligands for the selectins are mostly mucin-type glycoproteins. Increased expression and altered glycosylation of mucins are known to be prominent features of carcinoma progression. We have previously shown that all three selectins bind to colon carcinoma cell lines in a calcium-dependent fashion and that carcinoma growth and metastasis formation are attenuated in P-selectin-deficient mice. Here we show that the three recombinant soluble selectins recognize ligands within primary colon carcinoma tissue samples. Affinity chromatography showed that the ligands for all three selectins are O-sialoglycoprotease-sensitive mucins that are recognized in a calcium- and sialic acid-dependent manner. Furthermore, there are separate binding sites on the mucins for each selectin, allowing cross-binding of a single mucin molecule by more than one selectin. We also show that the selectin ligands on purified carcinoma mucins can mediate at least four different pathological interactions among platelets, leukocytes, and endothelial cells. These findings could explain some of the adhesive events of blood-borne tumor cells reported to occur with leukocytes, platelets, and endothelial cells, which are believed to play a part in modulating some early events in tumor metastases.

MeSH Terms
Animals Blood Platelets/metabolism,pathology Calcium/pharmacology Cell Communication Chromatography, Affinity Colonic Neoplasms/metabolism,pathology Dose-Response Relationship, Drug E-Selectin/metabolism Endothelium, Vascular/metabolism,pathology Enzyme-Linked Immunosorbent Assay Epithelial Cells/metabolism Humans Immunohistochemistry L-Selectin/metabolism Leukocytes/metabolism,pathology Ligands Mice Mice, Knockout Models, Biological Mucins/metabolism,pharmacology Neoplasm Transplantation P-Selectin/metabolism Selectins/physiology Thrombin/metabolism
Chemicals
E-Selectin Ligands Mucins P-Selectin Selectins L-Selectin Thrombin Calcium
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kim Y J
Glycobiology Research and Training Center, Division Hematology-Oncology, University of California San Diego, La Jolla, California, USA.
Borsig L
Han H L
Varki N M
Varki A
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)65142-5
Published
1999-08-00
Pages
461-72
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1866847
Subset
IM
Grants
NCI NIH HHS · R01 CA038701 · United States
NCI NIH HHS · CA38701 · United States
NCI NIH HHS · CA58689 · United States
External Links
PubMed source DOI: 10.1016/S0002-9440(10)65142-5 PMC Full Text View journal details
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