Anti-ANXA1 monoclonal antibody, clone 805DU3.3.2

Metastatic melanoma is one of the most aggressive forms of skin cancer and has a poor prognosis. We have previously identified Annexin A1 (ANXA1) as a potential murine melanoma-spreading factor that may modulate cell invasion by binding to formyl peptide receptors (FPRs). Here, we report that (1) in a B16Bl6 spontaneous metastasis model, a siRNA-induced decrease in tumoral ANXA1 expression significantly reduced tumoral MMP2 activity and number of lung metastases; (2) in a retrospective study of 61 patients, metastasis-free survival was inversely related to ANXA1 expression levels in primary tumors (HR 3.15 [1.03-9.69], p = 0.045); (3) in human melanoma cell lines, ANXA1 level was positively correlated with in vitro invasion capacity whereas normal melanocytes contained low ANXA1 levels, and (4) the ANXA1 N-terminal peptide ANXA1(2-26) stimulated MMP2 activity after interaction with FPRs and significantly stimulated the in vitro invasion of melanomas by acting on FPRs. These findings identify ANXA1 as a proinvasive protein in melanoma that holds promise as a potential prognostic marker and therapeutic target.

Annexins are a superfamily of calcium-dependent phospholipid-binding proteins that are implicated in a wide range of biological processes. The annexin superfamily comprises 13 members in humans (ANXAs), the majority of which are frequently dysregulated in cancer. However, the expression patterns and prognostic values of ANXAs in liver cancer are currently largely unknown. The present study aimed to analyze the expression levels of ANXAs and survival data in patients with liver cancer from the Oncomine, GEPIA, Kaplan-Meier plotter and cBioPortal for Cancer Genomics databases. The results demonstrated that ANXA1, A2, A3, A4 and A5 were upregulated, whereas ANXA10 was downregulated in liver cancer compared with normal liver tissues. The expression of ANXA10 was associated with pathological stage. High expression levels of ANXA2 and A5 were significantly associated with poor overall survival (OS) rate whereas ANXA7 and A10 were associated with increased OS. The prognostic values of ANXAs in liver cancer were determined based on sex and clinical stage, which revealed that ANXA2, A5, A7 and A10 were associated with OS in male, but not in female patients. In addition, the potential biological functions of ANXAs were identified by Gene Ontology functional annotation and Kyoto Encyclopedia of Genes Genomes pathway analysis; the results demonstrated that ANXAs may serve a role in liver cancer through the neuroactive ligand-receptor interaction pathway. In conclusion, the results of the present study suggested that ANXA1, A2, A3, A4, A5 and A10 may be potential therapeutic targets for liver cancer treatment, and that ANXA2, A5, A7 and A10 may be potential prognostic biomarkers of liver cancer.