MSMB variation and prostate cancer risk: Clues towards a possible fungal etiology

Abstract

BACKGROUND With recent advances in high-throughput sequencing technologies, many prostate cancer risk loci have been identified, including rs10993994, a single nucleotide polymorphism (SNP) located near the MSMB gene. Variant allele (T) carriers of this SNP produce less prostate secretory protein 94 (PSP94), the protein product of MSMB, and have an increased risk of prostate cancer (approximately 25% per T allele), suggesting that PSP94 plays a protective role in prostate carcinogenesis, although the mechanisms for such protection are unclear. METHODS We reviewed the literature on possible mechanisms for PSP94 protection for prostate cancer. RESULTS One possible mechanism is tumor suppression, as PSP94 has been observed to inhibit cell or tumor growth in in vitro and in vivo models. Another novel mechanism, which we propose in this review article, is that PSP94 may protect against prostate cancer by preventing or limiting an intracellular fungal infection in the prostate. This mechanism is based on the recent discovery of PSP94’s fungicidal activity in low-calcium environments (such as the cytosol of epithelial cells), and accumulating evidence suggesting a role for inflammation in prostate carcinogenesis. We provide further details of our proposed mechanism in this review article. CONCLUSIONS To explore this mechanism, future studies should consider screening prostate specimens for fungi using the rapidly expanding number of molecular techniques capable of identifying infectious agents from the entire tree of life.

The sea cucumber genome provides insights into morphological evolution and visceral regeneration

“…Further analysis on the translated amino acid sequences of these genes showed that they all had a domain that was analogous to the prostatic secretory protein of 94 amino acids (PSP94) based on the topological similarities of the cysteine residues, so we designated them as PSP94-like genes (Fig 6C). It was reported that the PSP94 genes in vertebrates underwent rapid evolution, which resulted in an improvement of their functions in a wide range of biological activities, such as inhibition of tumor growth [46], activation of immunity [47], and mesoderm formation [48]. Taken together, their specific arrangement pattern and distinguished expression profiles strongly suggested that the PSP94-like genes might play a vital role in the regenerative abilities of A .…”

pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

“…In particular, psoriasin possesses a histidine residue in its C-terminal region [127] similar to amoebapore A [82] and based on these similarities, it can be speculated that the enhanced action of psoriasin against B. megaterium at low pH may involve a histidine mediated increased ability for pore formation and oligomerisation. β-microseminoprotein (MSP), also named as PSP-94, is a human protein that is believed to have a protective role in prostate carcinogenesis due to its ability to suppress the growth of tumors although more recent studies have suggested that MSP may protect against prostate cancer by inhibiting fungal infection in this genital region [134,135]. This suggestion was primarily based on recent work, which showed that the acid conditions of the vagina promoted the ability of MSP in post coital seminal plasma to kill Candidia albicans .…”

Screening for chronic prostatitis pathogens using high‐throughput next‐generation sequencing

“…Fungal infections of the prostate are rare and primarily occur in immunocompromised patients. Sutcliffe et al 19 suggested that to screen for fungi in prostate specimens and explore their mechanism of action, future research should consider using rapidly advancing molecular techniques. Therefore, we used high‐throughput next‐generation sequencing technology to detect the gene sequences of all eukaryotic microorganisms in the specimens.…”