Alpha integrin subunits regulate human (Caco-2) intestinal epithelial proliferation and phenotype.
OBJECTIVE
Cell-matrix interactions influence intestinal epithelial biology, but the whether specific integrin heterodimers exert different effects is unclear.


METHODS
We used functional antibodies to investigate effects of the alpha2, alpha3, alpha5, and alpha6 integrin subunits on proliferation and differentiation of human intestinal Caco-2 cells on laminin. Cells seeded onto laminin-coated inserts in defibronectinized medium were treated with functional antibodies or normal IgG for 72 hrs and proliferation, alkaline phosphatase and dipeptidyl dipeptidase specific activity were measured.


RESULTS
Caco-2 adhesion to antibody to each alpha-integrin subunit stimulated tyrosine phosphorylation of Focal Adhesion Kinase and paxillin, suggesting that these antibodies intiate integrin-related tyrosine signalling. Proliferation was inhibited by anti-alpha2 and anti-alpha3, but stimulated by anti-alpha6. Alkaline phosphatase and dipeptidyl dipeptidase specific activity were promoted by alpha2 blockade but decreased after a6 blockade. Proliferative blockade using mitomycin C or hydroxyurea prevented the effects of alpha2 ligation on differentiation, but the decrease in alkaline phosphatase specific activity observed after a6 integrin subunit blockade was preserved even after proliferative blockade.


CONCLUSIONS
lntegrin heterodimers modulate human Caco-2 intestinal epithelial biology on laminin in an alpha-subunit specific manner. The different effects of anti-alpha2 and anti-alpha6 may reflect competitition by these antibodies with integrin subunit interactions with laminin as well as initiation of their own signals or different functions for the alpha6 integrin subunit
Basson
M D
MD
Depts. of Surgery, Yale University School of Medicine and CT VA Health Care System, New Haven and West Haven, CT 06520, USA. marc.basson@yale.edu
Emenaker
N J
NJ
Sanders
M A
MA
D000906:Antibodies / Q000276:immunology; D018938:Caco-2 Cells; D002455:Cell Division / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology; D006801:Humans; D016023:Integrins / Q000276:immunology / Q000502:physiology*; D007422:Intestines / Q000166:cytology*; D010641:Phenotype; D015398:Signal Transduction / Q000502:physiology
D000906:Antibodies; D016023:Integrins