MUC1 expressed in PanC1 cells decreases adhesion to type 1 collagen but increases contraction in collagen lattices.
A subline of human pancreatic cells (PanC1) that expresses low levels of cytokeratins 8 and 18 but not MUC1 mucin was transfected with both 3.5-kb and 3.9-kb full-length MUC1 cDNA. The MUC1-positive clone expressing the larger mucin was shown to express increased levels of cytokeratins 8 and 18 compared with the parental line or vector controls. Growth of these MUC1-transfected cells in type I collagen gels produced marked gel contraction that could be significantly reduced by the synthetic peptide SRGDTG or by growth in serum and fibronectin-depleted media. Cellular binding to type I collagen was found to be reduced by two- to four-fold in cells expressing the MUC1 mucin, for which the greatest inhibition was observed in cells expressing the larger form. No difference in cellular binding to fibronectin was observed. From these data we conclude that the human MUC1 mucin modifies the differentiated state of human pancreatic cells by altering cytokeratin expression and reducing adhesion to type I collagen but paradoxically enhancing the cellular contractile phenotype, effects that appear to be mediated by integrin expression and/or function.
Hudson
M J
MJ
Department of Histopathology, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
Stamp
G W
GW
Hollingsworth
M A
MA
Pignatelli
M
M
Lalani
E N
EN
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology; D003094:Collagen / Q000494:pharmacology* / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology; D005353:Fibronectins / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000378:metabolism; D018396:Mucin-1 / Q000502:physiology*; D009363:Neoplasm Proteins / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured
D005353:Fibronectins; D018396:Mucin-1; D009363:Neoplasm Proteins; D007633:Keratins; D003094:Collagen