Please note that eDoc will be permanently shut down in the first quarter of 2021!      Home News About Us Contact Contributors Disclaimer Privacy Policy Help FAQ

Quick Search
My eDoc
Session History
Support Wiki
Direct access to
document ID:

          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Publikationen des W. G. Kerckhoff-Instituts     Display Documents

ID: 474522.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
Inhibition of Urokinase Activity Reduces Primary Tumor Growth and Metastasis Formation in a Murine Lung Carcinoma Model
Authors:Henneke, I.; Greschus, S.; Savai, R.; Korfei, M.; Markart, P.; Mahavadi, P.; Schermuly, R. T.; Wygrecka, M.; Sturzebecher, J.; Seeger, W.; Gunther, A.; Ruppert, C.
Date of Publication (YYYY-MM-DD):2010
Title of Journal:Am J Respir Crit Care Med
Audience:Not Specified
Abstract / Description:RATIONALE: Lung cancer is the most common malignancy in humans. Urokinase (uPA) plays a crucial role in carcinogenesis by facilitating tumor cell invasion and metastasis. OBJECTIVES: We investigated the effect of the highly specific urokinase inhibitor CJ-463 (benzylsulfonyl-D-Ser-Ser-4-amidinobenzylamide) on tumor growth, metastasis formation and tumor vascularization in the murine Lewis lung carcinoma (LLC) and a human small lung cancer model. METHODS: 3x 10(6) LLC-cells were subcutaneously injected with into the right flank of C57Bl6/N mice, uPA knock out and uPAR knock out mice. Seven days later mice were randomized to receive i.p. either saline (control group), CJ-463 (10, 100mg/kg, twice a day), or its ineffective stereoisomer (10mg/kg, twice a day). Tumor volume was measured every second day and metastasis formation was monitored by volumetric-computed tomography. 12 days after onset of treatment mice were sacrificed and tumors were prepared for histological examination. MEASUREMENTS AND MAIN RESULTS: Treatment with CJ-463 resulted in a significant inhibition of primary tumor growth, with the highest efficacy seen in the 100mg/kg group. In addition, histological analysis of the lung revealed a significant reduction in lung micrometastasis in the 100mg/kg group. Similarly, a reduced seeding of tumor cells into the lung after i.v. injection of LLC cells was observed in inhibitor-treated mice. In these mice, treatment with CJ-463 appeared not to significantly alter the relative extent of tumor vascularization. In vitro, proliferation of LLC-cells remained unchanged upon inhibitor treatment. CJ-463 was found to similarly reduce tumor growth in uPAR knockout mice, but was ineffective in uPA knockout mice. CONCLUSIONS: Our results suggest that synthetic low molecular weight uPA-inhibitors offer as novel agents for treatment of lung cancer.
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:University of Giessen Lung Center(UGLC), Department of Internal Medicine, Medical Clinic II, Giessen, Germany.
Identifiers:ISSN:1535-4970 (Electronic) 1073-449X (Linking)
The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.