Human Beta Defensins and Cancer: Contradictions and Common Ground

Abstract

Human beta-defensins (hBDs, -1, 2, 3) are a family of epithelial cell derived antimicrobial peptides (AMPs) that protect mucosal membranes from microbial challenges. In addition to their antimicrobial activities, they possess other functions; e.g., cell activation, proliferation, regulation of cytokine/chemokine production, migration, differentiation, angiogenesis, and wound healing processes. It has also become apparent that defensin levels change with the development of neoplasia. However, inconsistent observations published by various laboratories make it difficult to reach a consensus as to the direction of the dysregulation and role the hBDs may play in various cancers. This is particularly evident in studies focusing on oral squamous cell carcinoma (OSCC). By segregating each hBD by cancer type, interrogating methodologies, and scrutinizing the subject cohorts used in the studies, we have endeavored to identify the "take home message" for each one of the three hBDs. We discovered that (1) consensus-driven findings indicate that hBD-1 and-2 are down- while hBD-3 is up-regulated in OSCC; (2) hBD dysregulation is cancer-type specific; (3) the inhibition/activation effect an hBD has on cancer cell lines is related to the direction of the hBD dysregulation (up or down) in the cancer from which the cell lines derive. Therefore, studies addressing hBD dysregulation in various cancers are not generalizable and comparisons should be avoided. Systematic delineation of the fate and role of the hBDs in a specific cancer type may lead to innovative ways to use defensins as prospective biomarkers for diagnostic/prognostic purposes and/or in novel therapeutic modalities.

Keywords: cancer; hBD-1; hBD-2; hBD-3; migration; proliferation.

Figure 1

(A) HBD-1,-2, and−3 either increased (red arrow) or decreased (green arrow) in cancers from different anatomical locations within human body (as indicated). (B) HBD-1,-2, and−3 either promote (red arrow) or inhibit (green arrow) migration/proliferation of cancers cells derived from different anatomical locations (as indicated). (C) Effector molecules/pathways by which each of the three defensins (hBD-1,−2, and−3) are dysregulated in cancers.