THROMBOSPONDIN (TSP) AND TRANSFORMING GROWTH-FACTOR-BETA-1 (TGF-BETA) PROMOTE HUMAN A549 LUNG-CARCINOMA CELL PLASMINOGEN-ACTIVATOR INHIBITOR TYPE-1 (PAL-1) PRODUCTION AND STIMULATE TUMOR-CELL ATTACHMENT IN-VITRO

被引:45
作者
ALBO, D
ARNOLETTI, JP
CASTIGLIONI, A
GRANICK, MS
SOLOMON, MP
ROTHMAN, VL
TUSZYNSKI, GP
机构
[1] MED COLL PENN,DEPT MED,PHILADELPHIA,PA 19129
[2] MED COLL PENN,DEPT SURG PLAST,PHILADELPHIA,PA 19129
关键词
D O I
10.1006/bbrc.1994.2262
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A growing body of evidence has recently implicated TSP and TGF-beta in the process of malignancy, such as tumor cell proliferation, tumor angiogenesis, and metastasis. The purpose of the present study was to evaluate potential mechanisms of TSP and TGF-beta in tumor cell attachment and invasion. Our results indicate that both TSP and TGF-beta promoted tumor cell attachment and spreading in the presence of plasminogen. The mechanism for these effects appeared to be due, in part, to the capacity of TSP and TGF-beta to induce tumor cell production of (PAI-1). PAI-1, which is a natural inhibitor of tumor-cell associated urokinase-type plasminogen activator (uPA) activity, inhibited activation of plasminogen to plasmin in the growth media,thereby preventing plasmin-induced detachment of cells. The TSP-promoted production of PAI-1 could be inhibited not only by anti-TSP antibodies but also by a neutralizing antibody against TGF-beta. These results suggest that TSP by a mechanism involving TGF-beta can promote cell adhesion through stimulation of tumor cell secretion of PAI-1. These data provide evidence that TSP not only has the capacity of functioning as a matrix protein to directly promote cell-substratum adhesion but that TSP can also stimulate cell adhesion and spreading by modulating cell surface protease expression through stimulation of tumor-associated production of PAI-1. (C) Academic Press, Inc.
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页码:857 / 865
页数:9
相关论文
共 38 条
[1]   THROMBIN-SENSITIVE PROTEIN OF HUMAN PLATELET MEMBRANES [J].
BAENZIGE.NL ;
BRODIE, GN ;
MAJERUS, PW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1971, 68 (01) :240-+
[2]  
BAENZIGER NL, 1972, J BIOL CHEM, V247, P2723
[3]   SPECIFIC-INHIBITION OF ENDOTHELIAL-CELL PROLIFERATION BY THROMBOSPONDIN [J].
BAGAVANDOSS, P ;
WILKS, JW .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1990, 170 (02) :867-872
[4]  
BENEZRA D, 1993, INVEST OPHTH VIS SCI, V34, P3601
[5]   ANTISENSE-MEDIATED REDUCTION IN THROMBOSPONDIN REVERSES THE MALIGNANT PHENOTYPE OF A HUMAN SQUAMOUS CARCINOMA [J].
CASTLE, V ;
VARANI, J ;
FLIGIEL, S ;
PROCHOWNIK, EV ;
DIXIT, V .
JOURNAL OF CLINICAL INVESTIGATION, 1991, 87 (06) :1883-1888
[6]  
CLEZARDIN P, 1991, CANCER RES, V51, P2621
[7]  
GASIC GJ, 1986, INT REV EXP PATHOL, V29, P173
[8]  
HOSOKAWA T, 1993, ONCOL RES, V5, P183
[9]   THROMBOSPONDIN EXERTS AN ANTIANGIOGENIC EFFECT ON CORD FORMATION BY ENDOTHELIAL-CELLS INVITRO [J].
IRUELAARISPE, ML ;
BORNSTEIN, P ;
SAGE, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (11) :5026-5030
[10]  
JAFFE EA, 1985, BLOOD, V65, P79