Characterization of the glycosylation profile of the human breast cancer cell line, MDA-231, and a bone colonizing variant.
The mechanisms that guide organ-specific metastases are not fully established. The aberrant expression of carbohydrates may play a fundamental role in defining the molecular mechanisms for metastases to distant organs and facilitate positive interactions within the target organ. The purpose of the present study was to determine the glycomic profile of a variant of the MDA-MB-231 breast cancer cell line that colonizes the bone and to ascribe mechanistic functions mediated by carbohydrates that might correlate with clinical bone metastases. The carbohydrate expression profiles of osteolytic MDA-MET breast cancer cells and non-osteolytic parental MDA-MB-231 cells were determined. MDA-MET cells were derived from MDA-MB-231 cells by in vivo selection of metastatic bone lesions following intracardiac inoculation. The two related breast cancer cell lines expressed distinct carbohydrate profiles; MDA-MET cells displayed an increased expression of alpha (2,6) linked sialic acid, N-beta1-6 GlcNAc, and sialylated Lewis-A antigen, and decreased expression of Galbeta1,3GalNAc as detected using a combination of lectins and anti-carbohydrate antibodies. Microarray analysis demonstrated an increased expression of glycosyltransferase genes, correlative for the distinct glycomic phenotype. The altered glycomic phenotypes of MDA-MET cells include effects on the differential binding to bone marrow endothelial cells, enhanced ECM binding and an increase in invasive potential. These data suggest that the glycomic phenotype of MDA-MET cells is associated with a select set of accumulated functions that collectively impact on the bone metastases and bone colonization capacity of breast cancer cells.
Carcel-Trullols
Jaime
J
Arkansas Cancer Research Center and Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Stanley
Joseph S
JS
Saha
Rinku
R
Shaaf
Saeid
S
Bendre
Manali S
MS
Monzavi-Karbassi
Behjatolah
B
Suva
Larry J
LJ
Kieber-Emmons
Thomas
T
D001854:Bone Marrow Cells / Q000166:cytology; D001859:Bone Neoplasms / Q000473:pathology / Q000556:secondary; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D002455:Cell Division; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D014644:Genetic Variation; D006031:Glycosylation; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis