Overexpression of MUC1 reconfigures the binding properties of tumor cells

Kimberly M. McDermott, Paul R. Crocker, Ann Harris, Michael D. Burdick, Yuji Hinoda, Toshiaki Hayashi, Kohzoh Imai, Michael A Hollingsworth

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Although it is known that adhesion and antiadhesion are essential to the metastatic spread of tumor cells, little is known about the molecules that regulate these processes. MUC1 is overexpressed and aberrantly glycosylated by a variety of tumor cells. Studies described here examined whether tumor-associated MUC1 conferred new binding properties on tumor cell lines. Flow cytometry analysis with soluble P-, E- and L-selectin/IgM chimeric proteins was performed on human pancreatic (S2-013 and Panc-I) and colon (Caco-2) tumor cells. S2-013 cells bound E- and P-selectin and Caco-2 cells bound P-selectin. Epitope-tagged MUC1 (MUCIF) expressed by S2-013, Panc-I and Caco-2 tumor cells did not bind to P-, E- or L-selectin. Overexpression of MUCIF on the surface of S2-013 cells blocked the interactions of E-selectin to tumor-associated ligand(s) but did not affect accessibility of monoclonal antibodies to other cell surface glycoproteins (CD9, CD44). Cell aggregation assays revealed that MUCIF expressed by S2-013 cells was able to bind to intracellular adhesion molecule-I expressed on B cells. Overexpression of MUCIF containing a targeted mutation (the tandem repeat domain entirely or partially deleted) did not block the binding of E-selectin to its S2-013-associated ligand. These results demonstrate for the first time that the heavily O-glycosylated tandem repeat domain of MUC1 can simultaneously mediate and block binding to adhesion molecules with some molecular specificity and further support the hypothesis that MUC1 plays a dual role in the metastatic spread of tumor cells.

Original languageEnglish (US)
Pages (from-to)783-791
Number of pages9
JournalInternational Journal of Cancer
Volume94
Issue number6
DOIs
StatePublished - Dec 15 2001

Fingerprint

E-Selectin
Caco-2 Cells
Neoplasms
L-Selectin
Tandem Repeat Sequences
P-Selectin
Ligands
Cell Aggregation
Membrane Glycoproteins
Tumor Cell Line
Cell Communication
Immunoglobulin M
Epitopes
Flow Cytometry
Colon
B-Lymphocytes
Monoclonal Antibodies
Mutation
Proteins

Keywords

  • Colon cancer
  • ICAM-1
  • Metastasis
  • Pancreatic cancer
  • Selectin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

McDermott, K. M., Crocker, P. R., Harris, A., Burdick, M. D., Hinoda, Y., Hayashi, T., ... Hollingsworth, M. A. (2001). Overexpression of MUC1 reconfigures the binding properties of tumor cells. International Journal of Cancer, 94(6), 783-791. https://doi.org/10.1002/ijc.1554

Overexpression of MUC1 reconfigures the binding properties of tumor cells. / McDermott, Kimberly M.; Crocker, Paul R.; Harris, Ann; Burdick, Michael D.; Hinoda, Yuji; Hayashi, Toshiaki; Imai, Kohzoh; Hollingsworth, Michael A.

In: International Journal of Cancer, Vol. 94, No. 6, 15.12.2001, p. 783-791.

Research output: Contribution to journalArticle

McDermott, KM, Crocker, PR, Harris, A, Burdick, MD, Hinoda, Y, Hayashi, T, Imai, K & Hollingsworth, MA 2001, 'Overexpression of MUC1 reconfigures the binding properties of tumor cells', International Journal of Cancer, vol. 94, no. 6, pp. 783-791. https://doi.org/10.1002/ijc.1554
McDermott KM, Crocker PR, Harris A, Burdick MD, Hinoda Y, Hayashi T et al. Overexpression of MUC1 reconfigures the binding properties of tumor cells. International Journal of Cancer. 2001 Dec 15;94(6):783-791. https://doi.org/10.1002/ijc.1554
McDermott, Kimberly M. ; Crocker, Paul R. ; Harris, Ann ; Burdick, Michael D. ; Hinoda, Yuji ; Hayashi, Toshiaki ; Imai, Kohzoh ; Hollingsworth, Michael A. / Overexpression of MUC1 reconfigures the binding properties of tumor cells. In: International Journal of Cancer. 2001 ; Vol. 94, No. 6. pp. 783-791.
@article{bb66c82fb8d54a83bb28211509641c49,
title = "Overexpression of MUC1 reconfigures the binding properties of tumor cells",
abstract = "Although it is known that adhesion and antiadhesion are essential to the metastatic spread of tumor cells, little is known about the molecules that regulate these processes. MUC1 is overexpressed and aberrantly glycosylated by a variety of tumor cells. Studies described here examined whether tumor-associated MUC1 conferred new binding properties on tumor cell lines. Flow cytometry analysis with soluble P-, E- and L-selectin/IgM chimeric proteins was performed on human pancreatic (S2-013 and Panc-I) and colon (Caco-2) tumor cells. S2-013 cells bound E- and P-selectin and Caco-2 cells bound P-selectin. Epitope-tagged MUC1 (MUCIF) expressed by S2-013, Panc-I and Caco-2 tumor cells did not bind to P-, E- or L-selectin. Overexpression of MUCIF on the surface of S2-013 cells blocked the interactions of E-selectin to tumor-associated ligand(s) but did not affect accessibility of monoclonal antibodies to other cell surface glycoproteins (CD9, CD44). Cell aggregation assays revealed that MUCIF expressed by S2-013 cells was able to bind to intracellular adhesion molecule-I expressed on B cells. Overexpression of MUCIF containing a targeted mutation (the tandem repeat domain entirely or partially deleted) did not block the binding of E-selectin to its S2-013-associated ligand. These results demonstrate for the first time that the heavily O-glycosylated tandem repeat domain of MUC1 can simultaneously mediate and block binding to adhesion molecules with some molecular specificity and further support the hypothesis that MUC1 plays a dual role in the metastatic spread of tumor cells.",
keywords = "Colon cancer, ICAM-1, Metastasis, Pancreatic cancer, Selectin",
author = "McDermott, {Kimberly M.} and Crocker, {Paul R.} and Ann Harris and Burdick, {Michael D.} and Yuji Hinoda and Toshiaki Hayashi and Kohzoh Imai and Hollingsworth, {Michael A}",
year = "2001",
month = "12",
day = "15",
doi = "10.1002/ijc.1554",
language = "English (US)",
volume = "94",
pages = "783--791",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "6",

}

TY - JOUR

T1 - Overexpression of MUC1 reconfigures the binding properties of tumor cells

AU - McDermott, Kimberly M.

AU - Crocker, Paul R.

AU - Harris, Ann

AU - Burdick, Michael D.

AU - Hinoda, Yuji

AU - Hayashi, Toshiaki

AU - Imai, Kohzoh

AU - Hollingsworth, Michael A

PY - 2001/12/15

Y1 - 2001/12/15

N2 - Although it is known that adhesion and antiadhesion are essential to the metastatic spread of tumor cells, little is known about the molecules that regulate these processes. MUC1 is overexpressed and aberrantly glycosylated by a variety of tumor cells. Studies described here examined whether tumor-associated MUC1 conferred new binding properties on tumor cell lines. Flow cytometry analysis with soluble P-, E- and L-selectin/IgM chimeric proteins was performed on human pancreatic (S2-013 and Panc-I) and colon (Caco-2) tumor cells. S2-013 cells bound E- and P-selectin and Caco-2 cells bound P-selectin. Epitope-tagged MUC1 (MUCIF) expressed by S2-013, Panc-I and Caco-2 tumor cells did not bind to P-, E- or L-selectin. Overexpression of MUCIF on the surface of S2-013 cells blocked the interactions of E-selectin to tumor-associated ligand(s) but did not affect accessibility of monoclonal antibodies to other cell surface glycoproteins (CD9, CD44). Cell aggregation assays revealed that MUCIF expressed by S2-013 cells was able to bind to intracellular adhesion molecule-I expressed on B cells. Overexpression of MUCIF containing a targeted mutation (the tandem repeat domain entirely or partially deleted) did not block the binding of E-selectin to its S2-013-associated ligand. These results demonstrate for the first time that the heavily O-glycosylated tandem repeat domain of MUC1 can simultaneously mediate and block binding to adhesion molecules with some molecular specificity and further support the hypothesis that MUC1 plays a dual role in the metastatic spread of tumor cells.

AB - Although it is known that adhesion and antiadhesion are essential to the metastatic spread of tumor cells, little is known about the molecules that regulate these processes. MUC1 is overexpressed and aberrantly glycosylated by a variety of tumor cells. Studies described here examined whether tumor-associated MUC1 conferred new binding properties on tumor cell lines. Flow cytometry analysis with soluble P-, E- and L-selectin/IgM chimeric proteins was performed on human pancreatic (S2-013 and Panc-I) and colon (Caco-2) tumor cells. S2-013 cells bound E- and P-selectin and Caco-2 cells bound P-selectin. Epitope-tagged MUC1 (MUCIF) expressed by S2-013, Panc-I and Caco-2 tumor cells did not bind to P-, E- or L-selectin. Overexpression of MUCIF on the surface of S2-013 cells blocked the interactions of E-selectin to tumor-associated ligand(s) but did not affect accessibility of monoclonal antibodies to other cell surface glycoproteins (CD9, CD44). Cell aggregation assays revealed that MUCIF expressed by S2-013 cells was able to bind to intracellular adhesion molecule-I expressed on B cells. Overexpression of MUCIF containing a targeted mutation (the tandem repeat domain entirely or partially deleted) did not block the binding of E-selectin to its S2-013-associated ligand. These results demonstrate for the first time that the heavily O-glycosylated tandem repeat domain of MUC1 can simultaneously mediate and block binding to adhesion molecules with some molecular specificity and further support the hypothesis that MUC1 plays a dual role in the metastatic spread of tumor cells.

KW - Colon cancer

KW - ICAM-1

KW - Metastasis

KW - Pancreatic cancer

KW - Selectin

UR - http://www.scopus.com/inward/record.url?scp=0035892304&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035892304&partnerID=8YFLogxK

U2 - 10.1002/ijc.1554

DO - 10.1002/ijc.1554

M3 - Article

VL - 94

SP - 783

EP - 791

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 6

ER -