Role of SLPI in Cancer. A number of studies have investigated the role of SLPI in cancer, both at the level of expression, and, more recently a number of studies addressing function have been published. SLPI expression is shown to be both up and down-regulated depending on tumour type (table.1.1). In many cases elevated SLPI expression has been reported, such as in lung cancers (Xxxxxxxx et al., 2000, Xxxx et al., 2006), ovarian cancer (Israeli et al., 2005, Xxxxx et al., 2001, Xxxxxxxx et al., 2002), pancreatic cancer (Xxxxxxxxx-Xxxxxxx et al., 2003, Xxx et al., 2002) and in one report, breast cancer, showing an overexpression (>2.5 fold) expression of SLPI in a highly metastatic breast cancer line compared to a poorly metastatic line (Xxxxxx et al., 2005). These data are suggestive that in certain contexts SLPI may be advantageous to tumour growth. However, there are an almost equal number of cancers where decreased SLPI expression has been observed, such as in nasopharengeal carcinoma (Xxxxx et al., 2012, Xxx et al., 2012, Xxxxxxxxxxx et al., 2004), melanoma (Xxxxxx et al., 2007, Xxxxxxx et al., 2011), and prostate (Xxxxxxxx et al., 2008), which is indicative of a potential tumour suppressor role in those tissues. In breast cancer, SLPI expression was shown to be down-regulated in one study (Xx et al., 2004) and in another its expression was linked to increased survival from disease (Xxxxxx et al., 2008). A further study showed that SLPI overexpression in breast cancer cell lines, increased apoptosis, and that intra-tumoural administration of SLPI in mice reduced tumour growth (Xxxxxx et al., 2012). In addition, inoculation of mice with mammary tumour cells over expressing SLPI reduced subsequent tumour growth (Xxxxxx et al., 2011). This contrasts with another study which shows mouse mammary tumour cells overexpressing SLPI have increased growth in vivo, but reduced invasiveness (Xxxxxx et al., 2007). This study also highlighted a potential role for SLPI in enhancing blood borne metastasis, though it provided no mechanistic insight as to how this metastatic advantage was mediated.
