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

Pawel Ciborowski, Olivera J. Finn

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)339-345
Number of pages7
JournalClinical and Experimental Metastasis
Volume19
Issue number4
DOIs
StatePublished - Jun 19 2002

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Immobilized Proteins
Tandem Repeat Sequences
Extracellular Matrix Proteins
Breast Neoplasms
Neoplasm Metastasis
Lung
Neoplasms
Peptides
In Vitro Techniques
Glycosylation
Ascites
Epitopes
Glycoproteins
Epithelial Cells

Keywords

  • Aberrant O-glycosylation
  • Breast cancer
  • Glycoprotein
  • Metastasis
  • Mucin
  • Synthetic MUC 1
  • Tn antigen

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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abstract = "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.",
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T1 - 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

T2 - Potential role in metastasis

AU - Ciborowski, Pawel

AU - Finn, Olivera J.

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N2 - 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.

AB - 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.

KW - Aberrant O-glycosylation

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