Prevention of metastasis by inhibition of the urokinase receptor.

Crowley, Craig; Cohen, Robert; Lucas, Brian K.; Liu, Guohui; Shuman, Marc A.; Levinson, Arthur D.

doi:10.1073/pnas.90.11.5021

Cited by 343 publications

(220 citation statements)

References 14 publications

Supporting

Mentioning

202

Contrasting

Order By: Relevance

“…As a result, a much greater fraction of the total energy is deposited in cells with alpha and very few nuclear hits are required to kill a cell. The expression of uPA/uPAR was found on a high percentage of human PC3 prostate cancer line (Crowley et al, 1993;Festuccia et al, 1998). Using immunocytochemistry and flow cytometry, we confirmed that uPA/uPAR was expressed on the surface of viable PC3 cells.…”

Section: Discussionmentioning

confidence: 99%

213Bi-PAI2 conjugate selectively induces apoptosis in PC3 metastatic prostate cancer cell line and shows anti-cancer activity in a xenograft animal model

Rizvi

Ranson

et al. 2002

Br J Cancer

View full text Add to dashboard Cite

A novel a-particle emitting ( 213 Bi) plasminogen activator inhibitor type 2 construct, which targets the membrane-bound urokinase plasminogen activator on prostate cancer cells, was prepared and evaluated in vitro and in a xenograft animal model. The PC3 prostate cancer cell line expresses urokinase plasminogen activator which binds to its receptor on the cell membrane; plasminogen activator inhibitor type 2 is bound to urokinase plasminogen activator/urokinase plasminogen activator receptor to form stable complexes. In vitro, the cytotoxicity of 213 Bi-plasminogen activator inhibitor type 2 against prostate cancer cells was tested using the MTS assay and apoptosis was documented using terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end-labelling (TUNEL) assay. In vivo, antiproliferative effects for tumours and prostate cancer lymph node metastasis were carried out in an athymic nude mouse model with a subcutaneous xenograft of PC3 cells. 213 Bi-plasminogen activator inhibitor type 2 was specifically cytotoxic to PC3 cells in a concentration-dependent fashion, causing the cells to undergo apoptosis. A single local or i.p. injection of 213 Bi-plasminogen activator inhibitor type 2 was able to completely regress the growth of tumours and lymph node metastases 2 days post subcutaneous inoculation, and obvious tumour regression was achieved in the therapy groups compared with control groups with 213 Bi-plasminogen activator inhibitor type 2 when the tumours measured 30 -40 mm 3 and 85 -100 mm 3 . All control animals and one of five (20%) mice treated with 3 mCi kg 71 213 Bi-plasminogen activator inhibitor type 2 developed metastases in the lymph nodes while no lymphatic spread of cancer was found in the 6 mCi kg 71 treated groups at 2 days and 2 weeks post-cell inoculation. These results demonstrate that this novel 213 Bi-plasminogen activator inhibitor type 2 conjugate selectively targets prostate cancer in vitro and in vivo, and could be considered for further development for the therapy of prostate cancer, especially for the control of micro-metastases or in minimal residual disease.

show abstract

Section: Discussionmentioning

confidence: 99%

213Bi-PAI2 conjugate selectively induces apoptosis in PC3 metastatic prostate cancer cell line and shows anti-cancer activity in a xenograft animal model

Rizvi

Ranson

et al. 2002

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…For example, intraperitoneal bolus injections of a human ATF-based antagonist has been shown to inhibit lung metastases of human tumor cells grown in athymic mice, with no significant effect on primary tumor growth. 9 In another study, intraperitoneal injections of peptides from murine ATF inhibited both primary tumor growth and dissemination. 10 Disruption of cell surface uPA/uPAR also inhibited bFGF-or VEGFinduced angiogenesis in an artificial bFGF-enriched extracellular matrix model.…”

Section: Introductionmentioning

confidence: 96%

“…Among them, the amino-terminal fragment of urokinase (ATF) is of particular interest because it can also exert a direct effect on the tumor cells and inhibit metastasis in experimental models. [9][10][11] Urokinase and its high affinity receptor, a GPI-anchored membrane protein (CD87), are believed to be critical elements in tumor biology because they control cell motility, tissue remodeling and the bioavailability of angiogenic factors. For example, uPA/uPAR complex formation at the cell surface is required for efficient activation of plasmin, a wide range protease that can degrade components of the basement membrane and the extracellular matrix (eg vitronectin, laminin, fibronectin), a prerequisite for tumor cell invasion.…”

Section: Introductionmentioning

confidence: 99%

Adenovirus-mediated delivery of a uPA/uPAR antagonist suppresses angiogenesis-dependent tumor growth and dissemination in mice

et al. 1998

View full text Add to dashboard Cite

AdmATF is a recombinant adenovirus encoding a secreted within and at the vicinity of the injection site was also supversion of the amino-terminal fragment (ATF) of murine pressed, suggesting that AdmATF inhibited primary tumor urokinase (uPA). This defective adenovirus was used in growth by targeting angiogenesis. AdmATF also interfered three murine models to assess the antitumoral effects with tumor cell establishment at distant sites: (1) lung disassociated with local or systemic delivery of ATF, a broad semination of Lewis lung carcinoma cells was significantly cell invasion inhibitor that antagonizes uPA binding to its reduced following intratumoral injection at the primary site; cell surface receptor (uPAR). A single intratumoral injection and (2) systemic administration of AdmATF inhibited subof AdmATF into pre-established MDA-MB-231 human sequent liver metastasis in a LS174T human colon carcibreast xenografts grown in athymic mice, or into pre-estabnoma xenograft model. These data outline the potential of lished C57/BL6 syngeneic Lewis lung carcinoma resulted using a recombinant adenovirus directing the secretion of an in a specific arrest of tumor growth. Neovascularization antagonist of cell-associated uPA for cancer gene therapy.

show abstract

“…UPAR and a5b1 induce EGFindependent but focal adhesion kinase-dependent EGF-R activation, generating high extracellular signalregulated protein kinase (ERK) and low p38 activity, conditions necessary for the growth of cancer cells in vivo (Aguirre-Ghiso et al, 1999, 2003Liu et al, 2002). Second, uPA and uPAR antagonists prevent not only invasiveness and metastasis dissemination but also tumor growth (Crowley et al, 1993;Min et al, 1996;Lakka et al, 2001;Ploug et al, 2001). Finally, a genetic screen in Ink4a À/À mice identified uPAR as a potential cooperating oncogene (Lund et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

A direct link between expression of urokinase plasminogen activator receptor, growth rate and oncogenic transformation in mouse embryonic fibroblasts

et al. 2006

View full text Add to dashboard Cite

In addition to its role in invasion and metastasis of several tumors, the multifunctional urokinase receptor uPAR (urokinase plasminogen activator receptor) is directly involved in the growth of several cancer cells in vitro and in vivo. We have compared growth rate and oncogenic transformation in wild-type (wt) or uPAR À/À mouse embryonic fibroblasts (MEFs). Surprisingly, uPAR À/À MEFs grew faster than wt MEFs. This agreed with elevated levels of cell cycle mediators like extracellular signal-regulated protein kinase, p38, AP1 and Cyclin D1. Infection with a uPAR retrovirus reverted the effect, decreasing the growth rate.When MEFs were transformed with H-Ras V12 and E1A oncogenes, the efficiency of transformation in uPAR À/À MEFs was higher than in wt. UPAR À/À MEFs grew faster at low serum, produced more colonies in agar and produced tumors in vivo in nude mice with a lower latency period. The properties of the heterozygous uPAR þ /À MEFs were always intermediate. We conclude therefore that in MEFs uPAR concentration controls cell proliferation and the transforming activity of some oncogenes.

show abstract

Prevention of metastasis by inhibition of the urokinase receptor.

Cited by 343 publications

References 14 publications

213Bi-PAI2 conjugate selectively induces apoptosis in PC3 metastatic prostate cancer cell line and shows anti-cancer activity in a xenograft animal model

213Bi-PAI2 conjugate selectively induces apoptosis in PC3 metastatic prostate cancer cell line and shows anti-cancer activity in a xenograft animal model

Adenovirus-mediated delivery of a uPA/uPAR antagonist suppresses angiogenesis-dependent tumor growth and dissemination in mice

A direct link between expression of urokinase plasminogen activator receptor, growth rate and oncogenic transformation in mouse embryonic fibroblasts

Contact Info

Product

Resources

About