Premium
Chondroitin sulfate glycosaminoglycans as major P‐selectin ligands on metastatic breast cancer cell lines
Author(s) -
MonzaviKarbassi Behjatolah,
Stanley J. Steven,
Hennings Leah,
Jousheghany Fariba,
Artaud Cecile,
Shaaf Saeid,
KieberEmmons Thomas
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22424
Subject(s) - glycosaminoglycan , metastatic breast cancer , chondroitin sulfate , metastasis , breast cancer , heparan sulfate , selectin , cancer research , chondroitin , cancer , medicine , chemistry , biochemistry , immunology , cell adhesion molecule
The metastatic breast cancer cell line, 4T1, abundantly expresses the oligosaccharide sialylated Lewis x (sLe x ). SLe x oligosaccharide on tumor cells can be recognized by E‐ and P‐selectin, contributing to tumor metastatic process. We observed that both selectins reacted with this cell line. However, contrary to the E‐selectin reactivity, which was sLe x dependent, P‐selectin reactivity with this cell line was sLe x ‐independent. The sLe x ‐Neg variant of the 4T1 cell line with markedly diminished expression of sLe x and lack of sLe a , provided a unique opportunity to characterize P‐selectin ligands and their contribution to metastasis in the absence of overlapping selectin ligands and E‐selectin binding. We observed that P‐selectin binding was Ca 2+ ‐independent and sulfation‐dependent. We found that P‐selectin reacted primarily with cell surface chondroitin sulfate (CS) proteoglycans, which were abundantly and stably expressed on the surface of the 4T1 cell line. P‐selectin binding to the 4T1 cells was inhibited by heparin and CS glycosaminoglycans (GAGs). Moreover, Heparin administration significantly inhibited experimental lung metastasis. In addition, the data suggest that surface CS GAG chains were involved in P‐selectin mediated adhesion of the 4T1 cells to murine platelets and human umbilical vein endothelial cells. The data suggest that CS GAGs are also the major P‐selectin‐reactive ligands on the surface of human MDA‐MET cells. The results warrant conducting clinical studies on the involvement of cell surface CS chains in breast cancer metastasis and evaluation of various CS types and their biosynthetic pathways as target for development of treatment strategies for antimetastatic therapy of this disease. © 2006 Wiley‐Liss, Inc.