Non-glycosylated tandem repeats of MUC1 facilitate attachment of breast tumor cells to normal human lung tissue and immobilized extracellular matrix proteins (ECM) in vitro: potential role in metastasis.
MUC1 is a transmembrane glycoprotein abundantly expressed on the apical surface of human ductal epithelial cells and over entire cell surface of tumors originating from those cells. It is 300 to 500 nm long and has a rigid, rod-like structure protruding from the cell surface. MUC1 expressed by normal cells has heavily O-glycosylated tandem repeat domain while MUC1 on malignant cells is aberrantly O-glycosylated. Substantially reduced (aberrant) glycosylation of the tandem repeat region of tumor MUC1 results in uncovering of the polypeptide core. This new structural feature may play an important role in the attachment of metastasizing tumor cells to tissues at distant sites. We show that MDA-MB-231 cells attaching to the immobilized extracellular matrix proteins (ECM) are higher MUC1 expressers than those non-attaching and that the attachment is inhibited by the addition of non-glycosylated, MUC1 peptide. This 100 a.a. peptide composed of 5 tandem repeats from the tandem repeat domain mimics the forms of MUC1 found in ascites fluid of cancer patients. We also show that this synthetic form of MUC1 inhibited attachment of breast tumor cells to sections of normal human lung tissue and immobilized ECM. We did not find correlation between the expression of Tn (GalNAc-Ser/Thr) epitope and the ability of tumor cells to adhere to the immobilized ECM. These results indicate that the non-glycosylated form of MUC1 plays a role in the initial attachment of carcinoma cells to tissues at distant sites, which may facilitate establishment of metastatic foci.
Ciborowski
Pawel
P
Department of Molecular Genetics & Biochemistry, School of Medicine, University of Pittsburgh, Pennsylvania, USA. pciborowski@earthlink.net
Finn
Olivera J
OJ
D000595:Amino Acid Sequence; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D006031:Glycosylation; D006801:Humans; D008168:Lung / Q000378:metabolism*; D018396:Mucin-1 / Q000737:chemistry* / Q000378:metabolism; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D020449:Repetitive Sequences, Amino Acid; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D016326:Extracellular Matrix Proteins; C116055:MUC1 tandem repeat peptide; D018396:Mucin-1; D009363:Neoplasm Proteins; D010446:Peptide Fragments