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Titolo:
Antibodies to PAI-1 alter the invasive and migratory properties of human tumour cells in vitro
Autore:
Brooks, TD; Slomp, J; Quax, PHA; De Bart, ACW; Spencer, MT; Verheijen, JH; Charlton, PA;
Indirizzi:
Xenova Grp Plc, Slough SL1 4NL, Berks, England Xenova Grp Plc Slough Berks England SL1 4NL lough SL1 4NL, Berks, England TNO PG, Gaubius Lab, Leiden, Netherlands TNO PG Leiden NetherlandsTNO PG, Gaubius Lab, Leiden, Netherlands
Titolo Testata:
CLINICAL & EXPERIMENTAL METASTASIS
fascicolo: 6, volume: 18, anno: 2001,
pagine: 445 - 453
SICI:
0262-0898(2001)18:6<445:ATPATI>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
PLASMINOGEN-ACTIVATOR INHIBITOR-1; TISSUE-TYPE; UROKINASE RECEPTOR; ENDOTHELIAL-CELLS; CARCINOMA-CELLS; BREAST-CANCER; MOUSE MODEL; VITRONECTIN; ADHESION; BINDING;
Keywords:
adhesion; invasion; migration; plasminogen activator inhibitor-1 (PAI-1); urokinase plasminogen activator (uPA);
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Brooks, TD Xenova Grp Plc, 957 Buckingham Ave, Slough SL1 4NL, Berks, England Xenova Grp Plc 957 Buckingham Ave Slough Berks England SL1 4NL
Citazione:
T.D. Brooks et al., "Antibodies to PAI-1 alter the invasive and migratory properties of human tumour cells in vitro", CLIN EXP M, 18(6), 2001, pp. 445-453

Abstract

Recent reports suggest that elevated levels of plasminogen activator inhibitor-1 (PAI-1) may contribute to tumour progression. The studies reported here were designed to help elucidate PAI-1's contribution to the invasive and migratory phenotype. Antibodies to PAI-1 dose-dependently, and significantly, inhibited the invasive and migratory potential of human HT1080 fibrosarcoma cells, as did an antibody to uPA and the plasmin inhibitor aprotinin. Invasion of the human melanoma cell line, BLM, was also attenuated by the anti-PAI-1 monoclonal antibody MAI-12. The non-invasive human melanoma cellline, IF6, which does not express uPA, provided further confirmation of PAI-1 and uPA's role as, upon transfection with uPA, this cell line attained an invasive phenotype, which was again attenuated by MAI- 12. Although antibodies to PAI-1 did not affect the adhesion of HT1080 cells to vitronectin,the antibody to uPA reduced their attachment. Addition of exogenous PAI-1,however, prevented HT1080 cell adhesion (IC50 180nM) and promoted cell detachment from vitronectin. Furthermore melanoma cells transfected with a uPAvariant, which had an impaired interaction with PAI-1, were not invasive and had impaired binding to vitronectin. These data highlight the importanceof a balanced proteolysis and suggest an additional role for PAI-1 distinct from its role in proteolysis. These data also suggest that uPA and PAI-1 may co-operate in the migratory process by respectively facilitating the attachment to, and subsequent detachment from, vitronectin in the extracellular matrix. These results support the clinical findings and indicate that modulation of PAI-1 activity may be of therapeutic benefit for the treatment of cancer.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/09/20 alle ore 13:40:15