Role of integrin alphavbeta3 in substrate-dependent apoptosis of human intestinal carcinoma cells.
Incubation of human intestinal carcinoma Caco-2 cells in suspension (i.e., in the absence of substrate contacts) leads to massive cell death by apoptosis. Since this type of apoptosis has been referred to as anoikis, we designated these cells as anoikis-positive. However, a minor proportion of Caco-2 cells, designated as anoikis-negative, survived in suspension. Extended incubation of the cells in suspension resulted in the reduction of the number of viable cells. In comparison to the original Caco-2 cell population, the anoikis-negative cells demonstrated markedly decreased levels of expression of integrin alphavbeta3 on the cell surface and of transcription of the alphav subunit gene. Activation of the signaling function of alphavbeta3 in the original Caco-2 cells led to substantial stimulation of anoikis, while the inhibition of expression of this receptor resulted in better resistance of the cells to anoikis. The data provide the first evidence that alphavbeta3 integrin can generate apoptosis-stimulating signals.
Morozevich
G E
GE
Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Moscow, 119992, Russia. berman@ibmh.msk.su
Kozlova
N I
NI
Chubukina
A N
AN
Berman
A E
AE
D023102:Anoikis; D017209:Apoptosis; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D005434:Flow Cytometry / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000235:genetics / Q000502:physiology*; D007414:Intestinal Neoplasms / Q000235:genetics / Q000473:pathology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011102:Polyhydroxyethyl Methacrylate / Q000494:pharmacology; D015398:Signal Transduction / Q000235:genetics; D013194:Staining and Labeling / Q000379:methods
D039302:Integrin alphaVbeta3; D016376:Oligonucleotides, Antisense; D011102:Polyhydroxyethyl Methacrylate