Expression of the beta 6 integrin subunit in development, neoplasia and tissue repair suggests a role in epithelial remodeling.
The alpha v beta 6 integrin was identified in cultured epithelial cells and functions as a fibronectin receptor. We have now used monoclonal antibodies to determine in vivo expression patterns of the beta 6 subunit in normal and pathological human or primate tissues, and during experimental wound healing or induced lung injury. The results indicate that beta 6 expression is restricted to epithelia and is up-regulated in parallel with morphogenetic events, tumorigenesis, and epithelial repair. During development of the kidney, lung, and skin, we found that beta 6 is expressed by specific types of epithelial cells, whereas it is mostly undetectable in normal adult kidney, lung and skin. In contrast, we detected high-level expression in several types of carcinoma. For example, beta 6 is almost invariably neo-expressed in squamous cell carcinomas derived from the oral mucosa, often focally localized at the infiltrating edges of tumor islands. Expression of beta 6 is also upregulated in migrating keratinocytes at the wound edge during experimental epidermal wound healing. Similarly, beta 6 expression is induced in type II alveolar epithelial cells during lung injury caused by injection of live bacteria. We also observed beta 6 expression in adult lungs and kidneys at focal sites of subclinical inflammation, as well as in a variety of clinical specimens from patients with chronic or acute inflammation of the lungs or kidneys. From these findings and earlier results, we hypothesize that alpha v beta 6 affects cell spreading, migration and growth during reorganization of epithelia in development, tissue repair, and neoplasia.
Breuss
J M
JM
Department of Medicine, University of California at San Francisco 94143, USA.
Gallo
J
J
DeLisser
H M
HM
Klimanskaya
I V
IV
Folkesson
H G
HG
Pittet
J F
JF
Nishimura
S L
SL
Aldape
K
K
Landers
D V
DV
Carpenter
W
W
D000818:Animals; D002455:Cell Division; D002465:Cell Movement; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism; D039641:Integrin beta Chains; D016023:Integrins / Q000032:analysis*; D007668:Kidney / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D008253:Macaca mulatta; D051379:Mice; D016513:Mice, SCID; D009369:Neoplasms / Q000378:metabolism*; D012867:Skin / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D014945:Wound Healing
D039641:Integrin beta Chains; D016023:Integrins; C072170:integrin beta6