Differential expression of trypsinogen and tumor-associated trypsin inhibitor (TATI) in bladder cancer

Abstract

Abstract. Tumor-associated trypsin inhibitor (TATI) is a marker of mucinous ovarian carcinoma, but it is also widely expressed in other malignant tumors and normal human tissues. Elevated serum concentrations of TATI are of prognostic value in ovarian, kidney, and bladder cancer. Tumor-associated trypsin is co-expressed with TATI in many malignancies and is thought to be involved in tumor invasion. TATI mRNA has been shown to be overexpressed in bladder cancer. We therefore studied whether trypsinogen expression also can be detected in bladder cancer and how this and TATI expression are associated with the clinicopathological characteristics of the tumors. We used RT-PCR, in situ hybridization and immunohistochemistry to detect trypsinogenand TATI mRNA and protein in tissue samples from 28 bladder cancer patients and ten benign urothelia. TATI expression was detected in all benign tissues and non-invasive tumors. However, the expression was lower in the muscle-invasive tumors (pT2; n=5), whereas trypsinogen expression was seen in all but one non-invasive tumor. We conclude that trypsinogen is expressed in both malignant and benign bladder epithelium, whereas TATI expression decreases with increasing stage and grade of the tumor. This may suggest that a balanced expression of TATI and trypsinogen is required in normal tissue and that this balance is disrupted during tumor progression.

High expression of tumour-associated trypsin inhibitor correlates with liver metastasis and poor prognosis in colorectal cancer

“…An elevated TATI expression has, with few exceptions, been associated with a more aggressive tumour phenotype and poor clinical outcome in several forms of cancer (Paju et al, 2004(Paju et al, , 2007Hotakainen et al, 2006;Lee et al, 2007;Tomlins et al, 2008). Given the frequently observed coexpression of TATI and trypsin in cancer, it can be hypothesised that increased levels of TATI reflect a simultaneous elevation of trypsin and, hence, increased propensity of the tumour cells to invade and spread.…”

“…In vitro, TATI increases cell migration and plays a role in tissue repair (Stenman, 1990). It has been suggested that expression of TATI and trypsin is balanced in normal tissue, but this balance could be disrupted during tumour progression (Hotakainen et al, 2006).…”

“…However, in most cancer forms, TATI and trypsin are coexpressed and show similar and adverse associations to disease outcome (Paju et al, 2004;Hotakainen et al, 2006). Elevated serum TATI has been shown to be a prognostic marker for ovarian cancer (Venesmaa et al, 1994(Venesmaa et al, , 1998, kidney cancer (Paju et al, 2001) and bladder cancer (Kelloniemi et al, 2003).…”

Editorial Comment on: Increased Expression of Tumor-Associated Trypsin Inhibitor, TATI, in Prostate Cancer and in Androgen-Independent 22Rv1 Cells

“…In deed trypsinogens are highly expressed in high grade prostate cancers, and not only by the luminal secretory cells but also by malignant cells, suggesting that trypsinogenes may be involved in promoting tumour growth and invasion [3]. As trypsinogen and TATI have been reported to be co-expressed in a variety of tumours including colorectal [8], ovarian [9] and bladder cancer [10,11] and it had previously been reported that expression of trypsinogens was associated with prostate cancer it seemed logical to investigate the role of TATI in prostate tumours. that trypsinogens and TATI may be involved in prostate cancer invasion and may also be of prognostic significance.…”

Role of the tumor-associated trypsin inhibitor SPINK1 in cancer development

“…8 In other tumors, low expression of SPINK1 is associated with adverse prognosis and aggressive disease, i.e., ventricular and bladder cancer. 9,10 In these tumors, SPINK1 may inhibit tumor invasion by inhibiting protease cascades involving trypsin. Recent studies have revealed another function of SPINK1, i.e., it can promote development and growth of prostate cancer by stimulating the epidermal growth factor receptor (EGFR).…”