Expression of urokinase-type plasminogen activator receptor in hepatocellular carcinoma

Abstract

hepatic metastasis in their resected liver have shown recurIt is well known that a urokinase-type plasminogen rence within 3 years, 9 prompting us to seek a new predictor activator receptor (uPAR) is a key protein in the plasfor this recurrence. minogen activation system, which plays a proteolyti-The metastatic process in malignant tumors involves local cally important role in the invasion and metastasis of invasion, intravasation, and extravasation. 10 These events various cancer cells. To assess the expression of uPAR depend on the tumor-associated proteolytic process including in hepatocellular carcinoma (HCC), we analyzed the exthe plasminogen activation system, and many reports have pression of uPAR messenger RNA (mRNA) and the proshown that the urokinase-type plasminogen activator (uPA) tein in 31 pair-samples of solitary HCC and nontumorous plays an important role in this process. 11-13 uPA is released liver tissues from the same patients. Fifteen samples exfrom tumor and stromal cells [14][15][16] in a single-chain zymogen hibited no histological potential of recurrence, such as form, pro-uPA. 17,18 pro-uPA is converted into a two-chain acportal involvement or intrahepatic metastasis (group A), tive form of uPA, which converts the ubiquitous zymogen and 16 samples exhibited such histological features plasminogen into the proteolytically active form, plasmin. (group B). Seventy-one percent of the cases showedPlasmin by itself degrades the extracellular matrix and actiuPAR signals, and these signals were mainly localized vates collagenases. 19 Some authors have described that poor at the cytoplasm of the tumor cells and tended to be at prognostic types of cancer cells show high levels of uPA. 20-22the front of invasive foci. 87.5% of the cases in group B The mechanism of the initial activation of pro-uPA under showed uPAR signals against 53.3% of the cases in group physiological conditions is unknown. uPA has a specific re-A (P õ .05). The rate of recurrence in the uPAR positive/ ceptor (uPAR) anchoring to the cell surface by glycosyl-phonegative cases in group A was 75.0% and 14.3%, respecphatidyl-inositol. [23][24][25][26][27] uPAR is a protein with an Mr55000-tively (P õ .05). In non-neoplastic cases, e.g., chronic ac-60000 (55-60 Kd molecular weight of uPAR antigen), tive hepatitis and cirrhosis, weak uPAR mRNA and protranslated from a 1.4-kb messenger RNA (mRNA) 28 and its tein signals were detected in hepatocytes neighboring amino-terminal domain has a high affinity with an epidermal the portal tracts, suggesting that this protein plays some growth factor-like domain in the pro-uPA and uPA molerole in such cases. The present study indicates that cules. 29,30 uPAR synthesis is regulated by growth factors such uPAR plays an important role at least in its initial stage as transforming growth factors b 1 and b 2 , epidermal growth in invasion and metastasis of HCC, and that uPAR exfactor, 31,32 and phorbol 12-myristate 13-acetate. 33 Binding of pression can be a candidate predictor of these factors.pro...

HGF, MET, and Matrix-Related Proteases in Hepatocellular Carcinoma, Fibrolamellar Variant, Cirrhotic and Normal Liver

“…u-PAR has also been documented in hepatocellular carcinoma (8,9,12). Our present study using immunohistochemical and western blot techniques corroborates the previous work.…”

Heparanase mRNA expression and point mutation in hepatocellular carcinoma

“…The chief components of GSG are heparan sulfate proteoglycans (HSPGs) that are principally composed of a core protein covalently linked to several heparan sulfate side chains [1] . Over the past ten years, most studies about neoplasm metastasis including HCC, focused on some proteases, such as matrix metalloproteinases (MMPs) [2][3][4] , u-PA [5,6] , serine and cysteine protease [7,8] whose substrates were structural proteins, but heparanase (HPA), whose substrate was GSGs, was ignored. In recent years, mammalian HPA gene has successfully been cloned and sequenced in Israel and U.S.A [9][10][11][12][13] , and HPA was found to play an important role in tumor invasion and metastasis.…”

Inhibitory Role of Plasminogen Activator Inhibitor‐1 in Invasion and Proliferation of HLE Hepatocellular Carcinoma Cells

“…14,15) On the other hand, PAI-1 suppresses metastasis in murine models of prostate carcinoma and melanoma. 16,17) We have reported that the plasminogen activation system is positively related to the invasion and postoperative recurrence of hepatocellular carcinoma (HCC), 18) suggesting that the inhibition of uPA-mediated proteolysis may contribute to the inhibition of HCC progression.…”