A Role for the Integrin αvβ8 in the Negative Regulation of Epithelial Cell Growth
2000
The control of cell growth is regulated through coordinated responses to
growth factors and cell-extracellular matrix (ECM) interactions.
Integrins, the major family of cell-ECM receptors, are vital to these
coordinated responses. Although much is known of the role of integrins
in growth promotion, specific examples of integrin-mediated cell growth
inhibition are few. On the basis of our findings that the integrin β8
subunit is expressed in airway epithelial cells and is absent in lung
cancers, we investigated the role and mechanism of the integrinα
vβ8 in mediating growth inhibition. When introduced into either a
lung or colon carcinoma cell line, β8 inhibited cell growth without
inducing apoptosis. Ligation of αvβ8 also induced cell rounding,
inhibited focal contact formation, and initiated an inhibitory
signaling pathway as demonstrated by increased expression of the
cyclin-dependent kinase inhibitor p21 Cip1 . The cytoplasmic
domain of β8 was capable of both growth inhibition and causing cell
shape changes as shown by the use of a chimeric integrin construct
consisting of the β8-cytoplasmic domain coupled to theβ
6-extracellular domain. Finally, when tested in vivo ,β
8 potently inhibited tumor growth in nude mice. Together, these
results implicate αvβ8 as a novel growth-regulatory molecule of
epithelial cells.
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