Restricted expression and function of laminin 1-binding integrins in normal and malignant oral mucosal keratinocytes
Abstract
Squamous cell carcinoma of the oral cavity spreads by initial invasion of the laminin-rich basement membrane. We examined the adhesion and motility of human oral SCC cells and normal mucosal keratinocytes and found that the SCC cells readily attached and migrated on laminin 1 substrates but migrated poorly on collagen type I and fibronectin. The normal keratinocytes, however, adhered poorly to and were non-motile on laminin 1 yet readily and preferentially attached and migrated on fibronectin and collagen type I. Analysis with blocking anti-integrin antibodies showed that the SCC cells used the alpha 6 beta 1 complex to attach and migrate on laminin 1 and that this activity was confined to the E8 long arm fragment of laminin. Affinity chromatography on laminin-Sepharose columns revealed that the SCC cells, but not normal keratinocytes, expressed high levels of the alpha 6 beta 1 laminin 1 receptor. Metabolic pulse-chase analysis indicated that in contrast to the SCC cells, keratinocytes did not have a stable pool of beta 1 subunit precursor. Preferential pairing of alpha 6 with beta 4 and the deficiency in pre-beta 1 levels appear to account for the failure of keratinocytes to form significant alpha 6 beta 1 complex. Additional...Continue Reading
References
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