Role of ps20 in cancer. Unlike elafin and SLPI the primary physiological function of ps20 has yet to be definitively elucidated. However, work published to date has implicated ps20 in range of processes including wound healing (Xxxxxxxx et al., 2006), ocular development (Xxxxxx et al., 2009), pre-eclampsia (Xxxxxxxxx et al., 2011), tumour suppression (Xxxxxxx et al., 2007), cellular senescence (Xxxxx et al., 2009) and an increase in susceptibility of CD4 T cells to HIV through regulation of adhesion molecule ICAM-1 (Xxxxxxx et al., 2011, Xxxxxxx et al., 2008). However, the biochemical complexities of ps20 and the lack of known binding partners continue to significantly hamper efforts understand this protein’s physiological significance in health and disease. ps20 was originally purified as a 20kDa factor from the culture media of rat urogenital sinus cells and was shown to potently inhibit proliferation of the PC-3 Prostate cancer cell line (Xxxxxx et al., 1995). Later, the same group cloned the WFDC1 gene (Xxxxxx et al., 1998) and located it to chromosome 16q24, a region which is subject to frequent mutation and loss in various cancers (Xxxxxx et al., 2000) (Xxxxxxxx et al., 2005). This protein is strikingly well conserved which suggests an important physiological role, but what this is exactly remains elusive. Further investigation into the biology of ps20 in prostate cancer demonstrated two important but contradictory phenomena. In a mouse xenograft model of prostate cancer, tumours formed from PC-3 cells engineered to overexpress rat-ps20 showed significant increase in size, dry weight, and micro-vascular density compared to control tumours (XxXxxxxx et al., 2003). Immunohistochemical analysis of this data showed significantly increased neo-vascularization in the ps20 tumour, suggesting a role in angiogenesis. Other experiments corroborated this, demonstrating that ps20 acts as a chemo-attractant, though not a growth factor, for endothelial cells and that ps20 expression was induced in prostate stromal cells by TGFβ (XxXxxxxx et al., 2003), a known angiogenic factor. This evidence suggests that despite being associated with a region of the chromosome often absent or mutated in tumours, that ps20 may also exert pro- tumourigenic characteristics under certain physiological conditions. In contrast, a subsequent study by the same group looked at ps20 expression in cancerous-prostate stromal and epithelial tissues from clinical samples using immunohistochemical analysis (XxXxxxxx ...
