Expression of beta 1, beta 3, beta 4, and beta 5 integrins by human lung carcinoma cells of different histotypes.
Structural and functional analyses of several integrin heterodimers were performed in non-small-cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cell lines. The expression of beta 1, beta 3, beta 4, and beta 5 heterodimers was evaluated at protein and mRNA levels. By flow cytometry and immunoprecipitation experiments we demonstrate that NSCLC cells (A549 adenocarcinoma and DG 3 large cell carcinoma) coexpress integrin heterodimers composed of beta 1, beta 3, beta 4, and beta 5 subunits, whereas SCLC cells (AE2 and H69) express only beta 1 integrin heterodimers. Northern blot experiments confirmed immunochemical analysis: SCLC cells in contrast to NSCLC cells express only the mRNA coding for the beta 1 subunit. These data indicate that in lung carcinoma cells the diversity in the integrin repertoire depends upon differential gene expression. The functionality of integrin receptors has been studied using antibody blocking experiments. Data reported demonstrate that the alpha 6 beta 1 integrin is a laminin receptor in either SCLC or NSCLC cells. An antibody to the beta 4 subunit partially inhibits the adhesion of adenocarcinoma cells to lamin but does not block lamin adhesion of large cell carcinoma cells, even though alpha 6 beta 4 complexes are expressed on both cell types. Two antisera to vitronectin receptors inhibit the adhesion of NSCLC cels to both vitronectin and fibronectin. The same antisera inhibit the adhesion of SCLC cells only to laminin, indicating that the alpha v beta 1 integrin might function in these cells as laminin receptor.
Falcioni
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Laboratorio Oncogenesi Molecolare, Istituto Regina Elena per lo studio e la cura dei tumori, Rome, Italy.
Cimino
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L
Gentileschi
M P
MP
D'Agnano
I
I
Zupi
G
G
Kennel
S J
SJ
Sacchi
A
A
D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D003094:Collagen / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008970:Molecular Weight; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000235:genetics; D019096:Vitronectin
D005353:Fibronectins; D006023:Glycoproteins; D016023:Integrins; D007797:Laminin; D012333:RNA, Messenger; D019096:Vitronectin; D003094:Collagen