Tumour-associated trypsin inhibitor (TATI) in ovarian cancer

Halila, Hannu; Lehtovirta, Pentti; Stenman, Ulf‐Hǎkan

doi:10.1038/bjc.1988.67

Cited by 49 publications

(32 citation statements)

References 14 publications

(19 reference statements)

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“…In a study comparing SPINK1 with several other markers, including CA125, SPINK1 was found to be particularly useful for diagnosis of ovarian cancer (16 ). During patient monitoring, the serum concentrations of SPINK1 reflect the development of recurrent disease (17 ). Compared to serum concentrations, up to 1000-fold higher concentrations of SPINK1 have been found in cyst fluid from both benign and malignant ovarian cysts, but increased serum concentrations are rare in patients with benign cysts (18 ).…”

Section: Ovarian Cancermentioning

confidence: 99%

“…Claudin-5 is a tight junction protein and its expression is associated with poor prognosis; it was suggested that claudin-5 could influence the expression of SPINK1 and CA125 but this remains to be investigated. Patients with ovarian cancer have higher SPINK1 concentrations in urine than in serum, but they correlate strongly if the urine concentrations are normalized according to urine creatinine or density (13,17 ). The interindividual variation in serum concentrations of SPINK1 are smaller and therefore serum measurements are preferred for follow-up of cancer patients (20 ).…”

Section: Ovarian Cancermentioning

confidence: 99%

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Emerging Roles of SPINK1 in Cancer

et al. 2016

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BACKGROUND Tumor-associated trypsin inhibitor (TATI) was originally isolated from the urine of a patient with ovarian cancer. It was later shown to be produced by many other tumors and several normal tissues. It had earlier been isolated from the pancreas and was hence called pancreatic secretory trypsin inhibitor (PSTI). It belongs to a family of protease inhibitors presently called serine peptidase inhibitor Kazal type (SPINK). In the SPINK family TATI/PSTI is SPINK1, which is the name used in this review. CONTENT In addition to being a protease inhibitor, SPINK1 also acts as an acute-phase reactant and a growth factor. Furthermore, it has been shown to modulate apoptosis. Overexpression of SPINK1 predicts an unfavorable outcome in several cancers and determination of SPINK1 in serum can be used to identify patients at increased risk of aggressive disease. Thus serum SPINK1 can be used as a prognostic tumor marker. Because SPINK1 acts as a growth factor and an inhibitor of apoptosis in some cancers, it has also been suggested that it can be a therapeutic target in cancer. However, because SPINK1 is the major physiological inhibitor of trypsin, inhibition of SPINK1 may increase the risk of pancreatitis. SUMMARY Taking into account the many functions of SPINK1, assessing the role of SPINK1 in cancer has several potentially important clinical applications ranging from a biomarker to a potential new target for cancer therapy.

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Section: Ovarian Cancermentioning

confidence: 99%

Section: Ovarian Cancermentioning

confidence: 99%

Emerging Roles of SPINK1 in Cancer

et al. 2016

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“…TATI in serum was measured by radioimmunoassay using reagents from Orion Diagnostica (Oulunsalo, Finland) as described previously (27). A cutoff value of 22 g/liter was used (36). Trypsinogen-2 (34) and trypsin-2-API (37) in serum were measured by timeresolved immunofluorometric assays as earlier described using cutoff values of 80 and 14 g/liter, respectively.…”

Section: Methodsmentioning

confidence: 99%

Expression of Trypsinogen-1, Trypsinogen-2, and Tumor-Associated Trypsin Inhibitor in Ovarian Cancer

Paju¹,

Vartiainen

Haglund

et al. 2004

Clinical Cancer Research

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Purpose:The purpose is to study the prognostic significance of tissue expression of trypsinogen-1, trypsinogen-2, and tumor-associated trypsin inhibitor (TATI) and serum concentration of trypsinogen-2, trypsin-2-API (complex of trypsin-2 with ␣-1-proteinase inhibitor), and TATI in epithelial ovarian cancer.Experimental Design: Expression of trypsinogen-1, trypsinogen-2, and TATI was determined by immunohistochemistry with monoclonal antibodies in tissue sections of tumors from 119 patients with untreated primary epithelial ovarian cancer. Preoperative serum concentrations of trypsinogen-2, trypsin-2-API and TATI were analyzed using specific immunoassays.Results: Fifty-four percent of the tumors expressed trypsinogen-1, 45% expressed trypsinogen-2, and 30% expressed TATI. In patients with stage III and IV disease, TATI tissue expression (P ‫؍‬ 0.002) and elevated TATI concentration in serum (P ‫؍‬ 0.048) were associated with adverse cancer-specific and progression-free survival in univariate analysis. In multivariate analysis, TATI tissue expression (P ‫؍‬ 0.005), tumor grade (P ‫؍‬ 0.0001), histological type (P ‫؍‬ 0.02), and stage (P ‫؍‬ 0.0005) were independent prognostic factors for adverse cancer-specific survival and TATI tissue expression (P ‫؍‬ 0.006) and grade (P ‫؍‬ 0.0003) for progression-free survival. In multivariate analysis of all patients and those with advanced disease, serum trypsin-2-API concentration was an adverse prognostic factor for cancer-specific and progression-free survival, and it was independent of stage and histological type of the tumor (P < 0.01).Conclusions: Tissue expression of TATI and an elevated preoperative serum concentration of trypsin-2-API are strong independent prognostic factors in advanced epithelial ovarian cancer. These results suggest that trypsin expression plays a role in the progression of ovarian cancer. TATI and trypsin-2-API are of potential use as an aid for stratification of randomized studies and for selecting treatment strategies.

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“…Tumour-associated trypsinogen is also known to be a serine protease produced by malignant tumour cells, and is believed to play an essential role in cancer invasion and metastasis by degrading trypsin-sensitive extracellular matrix components (Tryggvason et al, 1987;Koivunen et al, 1991a). Tumour-associated trypsinogen has been identified as a target protease for a tumour-associated trypsin inhibitor (TATI), also referred to as PSTI (Huhtala et al, 1982;Halila et al, 1988;Stenman et al, 1988). A recent study (Koivunen et al, 1989) has shown that tumourassociated trypsinogen and pancreatic trypsinogen are similar with respect to amino-terminal sequence, molecular weight and immunoreactivity, but that significant differences exist with respect to isoelectrophoretic mobility and stability.…”

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confidence: 99%

Pancreatic trypsinogen and cathepsin B in human pancreatic carcinomas and associated metastatic lesions

Ohta

Terada²,

Nagakawa³

et al. 1994

Br J Cancer

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Summary Expression of pancreatic trypsinogen and cathepsin B in 23 surgically resected pancreatic ductal adenocarcinomas was evaluated immunohistochemically, using a monoclonal antibody against human pancreatic trypsinogen and a polyclonal antibody against human cathepsin B. Fifteen of 20 invasive tubular adenocarcinomas (75%) expressed pancreatic trypsinogen in a coarse granular pattern located in the supranuclear cytoplasm of the carcinoma cells. In addition, metastatic lesions, including those in peripancreatic lymph nodes and neural plexuses, expressed pancreatic trypsinogen. In contrast, three intraductal (noninvasive) papillary adenocarcinomas did not express pancreatic trypsinogen. Cathepsin B expression was recognised in 14 of 20 invasive tubular adenocarcinomas (70%) in a fine granular pattern located diffusely in the cytoplasm of the carcinoma cells, while none of the three intraductal papillary adenocarcinomas had detectable cathepsin B. These findings suggest that pancreatic invasive ductal adenocarcinomas express pancreatic trypsinogen and cathepsin B immunoreactive peptides, raising the possibility that pancreatic trypsinogen and cathepsin B may act independently of each other in the process of carcinoma invasion and metastasis, like other different classes of proteases involved in the proteolytic modification of the matrix barrier.Pancreatic trypsinogen is one of the proteolytic enzymes produced by pancreatic acinar cells. A recent study (Miszczuk-Jamska et al., 1991) has shown that a new human pancreatic adenocarcinoma cell line (CFPAC-1) and a previously established human pancreatic carcinoma cell line (CAPAN-1) produce human pancreatic trypsinogen. This enzyme is a target protease for pancreatic secretory trypsin inhibitor (PSTI). Tumour-associated trypsinogen is also known to be a serine protease produced by malignant tumour cells, and is believed to play an essential role in cancer invasion and metastasis by degrading trypsin-sensitive extracellular matrix components (Tryggvason et al., 1987;Koivunen et al., 1991a). Tumour-associated trypsinogen has been identified as a target protease for a tumour-associated trypsin inhibitor (TATI), also referred to as PSTI (Huhtala et al., 1982;Halila et al., 1988;Stenman et al., 1988). A recent study (Koivunen et al., 1989) has shown that tumourassociated trypsinogen and pancreatic trypsinogen are similar with respect to amino-terminal sequence, molecular weight and immunoreactivity, but that significant differences exist with respect to isoelectrophoretic mobility and stability. Therefore, it is possible that pancreatic trypsinogen may also take part in the protease cascade associated with tumour invasion and metastasis. It is currently not known whether the differences between tumour-associated trypsinogen and pancreatic trypsinogen are a result of tissue-specific trypsinogen modification or distinct genes.We have therefore evaluated the presence or absence of pancreatic trypsinogen immunohistochemically in 23 surgically resected pancreatic ductal adeno...

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Tumour-associated trypsin inhibitor (TATI) in ovarian cancer

Cited by 49 publications

References 14 publications

Emerging Roles of SPINK1 in Cancer

Emerging Roles of SPINK1 in Cancer

Expression of Trypsinogen-1, Trypsinogen-2, and Tumor-Associated Trypsin Inhibitor in Ovarian Cancer

Pancreatic trypsinogen and cathepsin B in human pancreatic carcinomas and associated metastatic lesions

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