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Distinct ADAMs Selectively Inhibit Integrin-mediated Cell Migration

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Our results suggest that ADAM12 does not inhibit α4β1-mediated cell migration by altering the expression level of α4β1 integrin (Table 1). How might ADAMs influence integrin-mediated cell migration independent of proteolytic activity? Interestingly, a mutant allele of ADAM14 (UNC-71, a nonproteolytically active ADAM involved in two cell migration events in C. elegans) was found to have a substitution at the equivalent position (D504N) in its disintegrin loop. In this report, we studied the effects of four ADAMs on cell migration mediated by either the α4β1or α5β1 integrins.

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Collectively, the results presented in Figure 2 (using two different cell migration assays) indicate that ADAM12 inhibits cell migration on full-length FN mediated by the α4β1 but not by the α5β1 integrin. Expression of ADAM12 had no significant effect on the migration of Chinese hamster ovary (CHO) cells expressing α5β1 integrin on FN, as assessed using transwell (Figure 2, E and G) and scratch wound (Figure 2, F and H) assays. ADAM12 inhibits migration of α4β1- but not α5β1 integrin-expressing cells on fibronectin. From these photographs, the wound area (area not occupied by cells) was https://www.s4snextgen.org/ measured using Photoshop7.0 software, and percentage of wound closure was calculated as an indication of rate of cell migration. In this study we provide the first evidence that ADAMs can selectively modulate integrin-mediated cell migration.