These results indicate that cell differentiation selleck may be a determinant for the upregulation of epithelial hCAP18/LL-37 expression. Conversely, hCAP18/LL-37 is highly expressed in human breast cancer cells with a correlation between its peptide protein levels and tumor grade than normal mammary tissue [134]. In

addition, hCAP18/LL-37 is highly expressed in breast cancer, correlating with the expression of the ERBB2 gene; its peptide amplifies mitogen-activated protein kinase (MAPK) signaling through ErB2 and treatment with the LL-37 peptide stimulates migration of cancer cells [135]. Similarly, hCAP18/LL-37 is significantly overexpressed in ovarian cancer cells; its peptide induces ovarian cancer cell proliferation, migration, invasion, and matrix metalloproteinase

(MMP) activation through formyl peptide receptor-like 1 (FPRL1) signaling [136] and [137]. Furthermore, the hCAP18/LL-37 peptide is expressed mostly in human lung cancers. Overexpression of hCAP18/LL-37 in lung cancer xenografts increases the formation of significantly larger tumors in nude mice [138]. Collectively, these results suggest that hCAP18/LL-37 is an autocrine survival factor released by cancer cells. However, the involvement of hCAP18/LL-37 in human OSCC remains to be elucidated. Further study is needed to clearly understand this phenomenon. HDPs exhibit broad-range antimicrobial activity and a low probability of resistance development AZD0530 chemical structure [139]. They represent ideal potential therapeutics. However, several issues stand in the way of their development; the difficulty and high cost of manufacturing peptides is arguably the principal problem preventing the widespread clinical use of this class of antimicrobial therapeutics [140]. In the oral cavity, HDPs, including the hCAP18/LL-37 peptide, play important roles in maintaining

oral health. Therapeutic use of HDPs in oral care requires clinical studies with defined end points due to the complexity of the etiology and pathogenesis of oral complications. Human trials failed to support the use of isegenan (protegrin variant), as cathelicidin family peptide to reduce the Buspirone HCl severity of oral mucositis [141], although microbial limit testing and safety studies clearly indicated the efficacy of histatin in animals [142] and [143]. In addition, adsorption of histatin 5 onto a poly (methyl methacrylate) denture base can prevent C. albicans biofilm formation, thus serving to reduce denture-induced stomatitis [144]. Recently, it was shown that hCAP18/LL-37 potently inhibited the formation of Pseudomonas aeruginosa biofilms in vitro. This occurred at a very low and physiologically meaningful concentration of 0.5 μg/ml, far below that required to kill or inhibit growth [145]. Although lactoferrin (LF), an iron-binding glycoprotein, is originally identified as an HDP, in addition to antimicrobial activity and immunomodulatory functions, it also displays antitumor activity.