MUC1 Mediates Transendothelial Migration in vitro by Ligating Endothelial Cell ICAM-1

  • Jennifer J. Rahn
  • Jeffrey W. Chow
  • Garnet J. Horne
  • Brian K. Mah
  • Joanne T. Emerman
  • Pat Hoffman
  • Judith C. HughEmail author


MUC1 is a transmembrane glycoprotein expressed by normal breast epithelium and virtually all breast cancers. MUC1 is normally restricted to the apical surface of epithelia and loss of this polarized distribution in breast carcinomas is associated with lymph node metatases. Our previous work found that MUC1 can bind intercellular adhesion molecule-1 (ICAM-1), mediating adhesion of breast cancer cells to a simulated blood vessel wall, and also triggering a calcium-based signal in the MUC1-bearing cells. It is possible that the depolarized membrane distribution of MUC1 in breast carcinomas may facilitate interactions with stromal/endothelial ICAM-1 leading to adhesion and subsequent migration through the vessel wall. In the current study, we provide evidence that ICAM-1 can influence the migration of cells that express endogenous or transfected MUC1. Migration across a gelatin-coated Transwell membrane could be increased in a step-wise manner by the sequential addition of ICAM-1-expressing cells (endothelial cells and fibroblasts), and ICAM-1-inducing inflammatory cytokines (tumour necrosis factor-α and interleukin-1β). Antibodies against MUC1 or ICAM-1, but not a control antibody, could abrogate migratory increases. Cells that did not express MUC1 were unresponsive to ICAM-1. Our current findings build on our earlier work, by suggesting that the end result of the MUC1/ICAM-1-mediated cell–cell adhesion and calcium-based signal is migration. This has implications for the exit of circulating tumour cells from the vasculature, as well as tumour cell migration through fibroblast-containing stroma underlying the endothelial wall.


breast cancer ICAM-1 MUC1 transendothelial migration transwell assay 



Dulbecco’s minimal essential medium


Dulbecco’s phosphate buffered saline


endothelial cell growth supplement


enhanced chemiluminescence


epidermal growth factor receptor


extracellular signal-regulated kinase


fetal bovine serum


growth factor receptor-bound protein 2


glycogen synthase kinase-3β


human mammary epithelial cell


human umbilical vein endothelial cell


intercellular adhesion molecule-1


insulin-like growth factor




leukocyte common antigen


mitogen activated protein kinase


macrophage inflammatory protein 1


nitroblue tetrazolium chloride/5-bromo-4-chloro-3-indolyl phosphate, toluidine salt


proliferating cell nuclear antigen


primary human endothelial cell




protein kinase C δ


regulated upon activation, normal T-cell expressed and secreted


single-chain urokinase-type plasminogen activator


standard error of the mean


son of sevenless


signal sequence-YFP-MUC1


transendothelial migration, specifically extravasation


tumour necrosis factor α


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Copyright information

© Springer 2005

Authors and Affiliations

  • Jennifer J. Rahn
    • 1
  • Jeffrey W. Chow
    • 1
  • Garnet J. Horne
    • 1
  • Brian K. Mah
    • 1
  • Joanne T. Emerman
    • 2
  • Pat Hoffman
    • 3
  • Judith C. Hugh
    • 1
    Email author
  1. 1.Department of Laboratory Medicine and Pathology, Cross Cancer InstituteUniversity of AlbertaEdmontonCanada
  2. 2.Department of Cellular & Physiological Sciences, Faculty of MedicineUniversity of British ColombiaVancouverCanada
  3. 3.ICOS CorporationBothellUSA

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