Antimicrobial Peptides in Bladder Cancer

Introduction

Antimicrobial peptides are important components of the innate (non-specific) immune defense against microbial pathogens in a wide range of organisms including humans [1,2]. Mammalian cells secrete different kinds of AMPs, such as Human Beta-Defensins (HBD-1 or HBD-4) in the epithelium and leukocytes, histatins in saliva, and cathelicidins (CAP18 or CAMP) in neutrophils and the epithelium [3,4]. Mycobacteria trigger epithelial cells to express AMPs. AMPs have nonspecific cytotoxicity against a wide range of normal and malignant targets, and direct lyse mycobacteria by permeabilizing the cellular membranes [5,6]. Some bacteria protect themselves against AMPs by secreting special proteins that inhibit their function, such as Streptococcal İnhibitor of Complement (SIC) and D-Alanine: D-Alanyl carrier protein ligase (DltA) [7-10]. Bacillus Calmette-Guérin (BCG) is commonly used as the most effective immunotherapeutics for high-risk non-muscle-invasive bladder cancer patients. Although BCG is more effective than the other chemotherapies, innate immune responses involving Antimicrobial Peptides (AMPs) cause BCG failure and unwanted side effects. After intravesical application in the bladder, BCG first directly contacts with the bladder urothelium, and the second step is BCG uptake by bladder cancer cells (internalization), probably by endocytosis. The innate immune response acts against BCG to sterilize the urinary tract, and some of the effectors involved in this innate response to BCG are Antimicrobial Peptides (AMPs). It was shown that rBCG treatment induced higher secretion of AMPs by the bladder cancer cells compared to BCG treatment and rBCG exerts a direct anti-proliferative effect on human bladder cancer cells. Therefore, it is believed that the therapeutic efficacy of BCG could be maintained or improved with lower doses of rBCG without the severe side effects or infection associated with the administration of high-dose BCG.


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