Anti-ITGA5 (aa 803-832) polyclonal antibody

Vertebrate sensory organs develop in part from cranial placodes, a series of ectodermal thickenings that coalesce from a common domain of preplacodal ectoderm. Mechanisms coordinating morphogenesis and differentiation of discrete placodes are still poorly understood. We have investigated whether placodal assembly in zebrafish requires Integrin-alpha 5 (itga5), an extracellular matrix receptor initially expressed throughout the preplacodal ectoderm. Morpholino knockdown of itga5 had no detectable effect on anterior placodes (pituitary, nasal and lens), but posterior placodes developed abnormally, resulting in disorganization of trigeminal and epibranchial ganglia and reduction of the otic vesicle. Cell motion analysis in GFP-transgenic embryos showed that cell migration in itga5 morphants was highly erratic and unfocused, impairing convergence and blocking successive recruitment of new cells into these placodes. Further studies revealed genetic interactions between itga5 and Fgf signaling. First, itga5 morphants showed changes in gene expression mimicking modest reduction in Fgf signaling. Second, itga5 morphants showed elevated apoptosis in the otic/epibranchial domain, which was rescued by misexpression of Fgf8. Third, knockdown of the Fgf effector erm had no effect by itself but strongly enhanced defects in itga5 morphants. Finally, proper regulation of itga5 requires dlx3b/4b and pax8, which are themselves regulated by Fgf. These findings support a model in which itga5 coordinates cell migration into posterior placodes and augments Fgf signaling required for patterning of these tissues and cell survival in otic/epibranchial placodes.

Integrins are a large family of cell surface receptors that bind extracellular matrix proteins and participate in cancer progression. However, the prognostic value of integrin family genes in post-operative patients with HBV-related hepatocellular carcinoma (HCC) remains unknown. In this study, we investigated 18 single nucleotide polymorphisms (SNPs) in integrin family genes and found that the AG/GG genotypes at rs988574 in ITGA1 predicted a better prognosis compared to carriers of the AA genotype (P = 0.025, HR = 0.69, 95% CI = 0.50-0.96). Moreover, rs988574 genotype combined with serum level of AFP had a better prognostic value in HBV-related HCC patients (P = 0.026, HR = 1.75, 95% CI = 1.07-2.85). Furthermore, we compared the expression of 24 integrin family genes in HBV-related HCC tissues and adjacent normal tissues. Survival analysis demonstrated that expression of three of the family members, ITGA5, ITGB5 and ITGA2B, were significantly associated with the overall survival (OS) or relapse-free survival (RFS) of HBV-related HCC patients. Additionally, patients with lower expression of both ITGA5 and ITGB5 had the best OS and RFS (P = 0.017 and P = 0.002, respectively). Our study demonstrated that rs988574 of ITGA1 and the expression of ITGA5, ITGB5 and ITGA2B are potential independent prognostic bio-markers and therapeutic targets for HBV-related HCC patients and may be useful for the diagnosis of HBV-related HCC.