INHIBITION OF TUMOR-CELL INVASION BY VERAPAMIL

被引：26

作者：

YOHEM, KH ^{[1
]}

CLOTHIER, JL ^{[1
]}

MONTAGUE, SL ^{[1
]}

GEARY, RJ ^{[1
]}

WINTERS, AL ^{[1
]}

HENDRIX, MJC ^{[1
]}

WELCH, DR ^{[1
]}

机构：

[1] PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT PATHOL,HERSHEY,PA 17033

来源：

PIGMENT CELL RESEARCH | 1991年 / 4卷 / 5-6期

关键词：

CYTOSKELETON; EXPERIMENTAL METASTASES; TYPE-IV COLLAGENASE; MICROTUBULES; MICROFILAMENTS;

D O I：

10.1111/j.1600-0749.1991.tb00445.x

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Verapamil, a calcium channel antagonist, inhibits murine B16 melanoma and colon adenocarcinoma C26 tumor metastasis by altering platelet aggregation [Tsuruo, T., et al. (1985) Cancer Chemother. Pharmacol., 14:30-33]. However, the role of calcium homeostasis in regulating several biochemical pathways implicated in other steps of the metastatic cascade suggests that calcium channel antagonists could also inhibit metastasis by other mechanisms. In this report, non-toxic doses of verapamil reversibly decreased human A375M and C8161 melanoma cell invasion and metastasis in a dose-dependent manner. Verapamil reduced cellular invasion and metastases by up to 96% (range 78-96%). Concomitantly, verapamil disrupts microtubule and microfilament organization and inhibits unidirectional cell migration but does not affect cellular adhesion to endothelial monolayers or reconstituted basement membranes. In addition, tumor cells treated with verapamil have a decrease in mRNA of type IV collagenase, a proteinase important in tumor cell degradation of basement membranes. Collectively, these data offer additional evidence regarding the mechanisms of action of verapamil as an anti-metastatic agent.

引用

页码：225 / 233

页数：9

共 58 条

[1] METHOD FOR DETECTION OF SPECIFIC RNAS IN AGAROSE GELS BY TRANSFER TO DIAZOBENZYLOXYMETHYL-PAPER AND HYBRIDIZATION WITH DNA PROBES [J].

ALWINE, JC ;

KEMP, DJ ;

STARK, GR .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1977, 74 (12) :5350-5354

[2] 12-O-TETRADECANOYL-PHORBOL-13-ACETATE INDUCTION OF THE HUMAN COLLAGENASE GENE IS MEDIATED BY AN INDUCIBLE ENHANCER ELEMENT LOCATED IN THE 5'-FLANKING REGION [J].

ANGEL, P ;

BAUMANN, I ;

STEIN, B ;

DELIUS, H ;

RAHMSDORF, HJ ;

HERRLICH, P .

MOLECULAR AND CELLULAR BIOLOGY, 1987, 7 (06) :2256-2266

[3]

BERNHARD EJ, 1990, CANCER RES, V50, P3872

[4] HALF-LIFE OF SYNOVIAL CELL COLLAGENASE MESSENGER-RNA IS MODULATED BY PHORBOL-MYRISTATE ACETATE BUT NOT BY ALL-TRANS-RETINOIC ACID OR DEXAMETHASONE [J].

BRINCKERHOFF, CE ;

PLUCINSKA, IM ;

SHELDON, LA ;

OCONNOR, GT .

BIOCHEMISTRY, 1986, 25 (21) :6378-6384

[5]

BROWN PD, 1990, CANCER RES, V50, P6184

[6] ONCOGENES AND THE NATURE OF MALIGNANCY [J].

BUCKLEY, I .

ADVANCES IN CANCER RESEARCH, 1988, 50 :71-94

[7] ISOLATION OF BIOLOGICALLY-ACTIVE RIBONUCLEIC-ACID FROM SOURCES ENRICHED IN RIBONUCLEASE [J].

CHIRGWIN, JM ;

PRZYBYLA, AE ;

MACDONALD, RJ ;

RUTTER, WJ .

BIOCHEMISTRY, 1979, 18 (24) :5294-5299

[8] ENHANCED MOTILITY IN NIH-3T3 FIBROBLASTS THAT OVEREXPRESS GELSOLIN [J].

CUNNINGHAM, CC ;

STOSSEL, TP ;

KWIATKOWSKI, DJ .

SCIENCE, 1991, 251 (4998) :1233-1236

[9] RECEPTOR FUNCTIONS FOR THE INTEGRIN VLA-3 - FIBRONECTIN, COLLAGEN, AND LAMININ BINDING ARE DIFFERENTIALLY INFLUENCED BY ARG-GLY-ASP PEPTIDE AND BY DIVALENT-CATIONS [J].

ELICES, MJ ;

URRY, LA ;

HEMLER, ME .

JOURNAL OF CELL BIOLOGY, 1991, 112 (01) :169-181

[10]

FIDLER IJ, 1990, CANCER RES, V50, P6130

← 1 2 3 4 5 6 →