Rapid onset of apoptosis in vitro follows disruption of beta 1-integrin/matrix interactions in human colonic crypt cells.
OBJECTIVE
Apoptosis by loss of adherence is a recently described phenomenon termed "anoikis." beta 1, integrins are heterodimeric surface molecules mediating adhesion to the extracellular matrix. The aim of this study was to address whether anoikis accounts for the elimination of senescent enterocytes and, if so, whether beta 1 integrins are involved.


METHODS
Whole crypts were isolated from normal human colonic mucosa and examined in vitro.


RESULTS
The vast majority of cells in resuspended crypts rapidly underwent apoptosis within 4 hours. Apoptosis was partially inhibited when cells had contact with collagen I-coated membranes or when whole crypts were embedded in a collagen gel. Preincubation of crypts with an inhibiting anti-beta 1 antibody before readhesion caused a much higher apoptotic rate. Confocal microscopy of embedded crypts revealed two critical zones of high sensitivity to temporary loss of adherence: the base of the crypts where stem cells are supposed to reside and the crypt mouth including the surface epithelium.


CONCLUSIONS
Survival of colonic epithelia crucially depends on matrix adhesion and is likely to be guaranteed by beta 1-integrin/ matrix interaction. The data strongly suggest that anoikis is the way senescent colon cells die.
Sträter
J
J
Department of Pathology, University of Heidelberg, Germany.
Wedding
U
U
Barth
T F
TF
Koretz
K
K
Elsing
C
C
Möller
P
P
D017209:Apoptosis; D002448:Cell Adhesion; D002470:Cell Survival; D003106:Colon / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D046508:Culture Techniques; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism / Q000502:physiology; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism* / Q000502:physiology; D007413:Intestinal Mucosa / Q000166:cytology / Q000502:physiology; D015398:Signal Transduction
D016326:Extracellular Matrix Proteins; D019012:Integrin beta1