Enhanced expression of urokinase plasminogen activator and its receptor in pancreatic carcinoma

Abstract

Summary Urokinase plasminogen activator (uPA) is a serine proteinase that has been suggested to play an important role in cancer invasion and metastasis. It binds to a specific membrane receptor denominated uPA receptor (uPAR Pancreatic cancer has one of the poorest prognoses of all gastrointestinal malignancies, being the fourth or fifth leading cause of cancer-related deaths in Western industrialized countries (Bomman et al, 1994). Gudjonsson (1987), in his classical review of 37 000 patients with pancreatic cancer, demonstrated an overall survival rate of 0.4% and a median survival time of 5 months after the diagnosis was established. Once pancreatic cancer is clinically evident, it progresses at a rapid rate, and metastasis has usually occurred at the time of diagnosis. Consequently, many patients are not resectable at presentation, and the overall resection rate is often less than 30% (Gudjonsson 1987;Bomman et al, 1994). The mechanisms that regulate this aggressive growth behaviour in pancreatic cancer are not at all clear. Recently, it has been shown in pancreatic cancer that the concomitant overexpression of the epidermal growth factor (EGF) receptor and its ligands EGF-, TGF-alpha (Korc et al, 1992;Yamanaka et al, 1993a) and/or amphiregulin (Ebert et al, 1994a; Yokoyama et al., 1995a) is associated with shorter post-operative survival following tumour resection. In addition, enhanced expression of c-erbB-3 (Friess et al, 1995), TGF-fs and basic fibroblast growth

Generation of a recombinant Sendai virus that is selectively activated and lyses human tumor cells expressing matrix metalloproteinases

“…There is increasing evidence suggesting that the higher the protease level at diagnosis the worse the prognosis, 27,38 and we have shown here that there would be a critical threshold of the enzyme levels required for virus activation. Thus, not only the species but also the amounts of the proteases involved in the actual tumor will have to be included in 'individualization'.…”

Prognostic relevance of urokinase plasminogen activator detection in micrometastatic cells in the bone marrow of patients with primary breast cancer

“…High uPA and PAI-1 levels are correlated with a poor prognosis for patients with primary breast cancer (Duffy et al, 1990;Janicke et al, 1990Janicke et al, , 1993Foekens et al, 1992Foekens et al, , 1994Grondahl-Hansen, 1993). The PA system appears to be a strong prognostic marker in breast cancer as well as in other types of cancer (Nekarda et al, 1994;Pedersen et al, 1994;Cantero et al, 1997). Recently, the prognostic significance of the uPAR in breast cancer (Grondahl-Hansen, 1995), colorectal cancer (Ganesh et al, 1994), gastric cancer (Heiss et al, 1995b), pancreatic cancer (Cantero et al, 1997) and lung cancer (Pedersen et al, 1994) has been shown.…”

“…The PA system appears to be a strong prognostic marker in breast cancer as well as in other types of cancer (Nekarda et al, 1994;Pedersen et al, 1994;Cantero et al, 1997). Recently, the prognostic significance of the uPAR in breast cancer (Grondahl-Hansen, 1995), colorectal cancer (Ganesh et al, 1994), gastric cancer (Heiss et al, 1995b), pancreatic cancer (Cantero et al, 1997) and lung cancer (Pedersen et al, 1994) has been shown. While numerous studies have reported an increase in uPA expression during transmigration of basal membranes in extracellular matrix in metastatic and non-metastatic tumour cell lines, this has not previously been investigated in breast cancer cells that have already been shedded (Ossowski et al, 1991;Henderson et al, 1992).…”

Metastasis-associated Factors Facilitating the Progression of Colorectal Cancer

“…Specific inhibition of the u-PA receptor has been successful in reducing the establishment of primary tumors and metastasis after intravenous injection of tumor cells into immunodeficient mice (Ignar et al, 1998). In colorectal cancer, numerous studies have shown overexpression of u-PAR cell in contrast to the corresponding normal tissue and/or surrounding stromal cells (Cantero et al, 1997;Morita et al, 1998), and suggested u-PAR as a characteristic of the invasive or even the malignant phenotype (Sliutz et al, 1996). Colorectal cancer with a high uPAR expression has been correlated with a low 5-year survival (Ganesh et al, 1994).…”