|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 95 No. 10 (May 15), 2000:
pp. 3133-3138
Concentration-dependent dual effect of thrombin on impaired
growth/apoptosis or mitogenesis in tumor cells
Jasmine Zain,
Yao-Qi Huang,
XueSheng Feng,
Mary Lynn Nierodzik,
Jian-Jun Li, and
Simon Karpatkin
From New York University Medical School, Kaplan Cancer Center, and
Department of Veterans Affairs Medical Center, New York, NY.
Because thrombin-treated tumor cell-induced metastasis increases
tumor nodule volume12 greater than nodule number, we
studied the effect of thrombin on tumor cell growth in vitro and in
vivo (murine B16F10 melanoma, human HCT8 colon carcinoma, DU145
prostate carcinoma). Tumor cell growth was measured after 3 to 7 days
in 1% fetal calf serum (FCS) + RPMI 1640. We found that, whereas
relatively low concentrations of thrombin, 0.1 to 0.5 U/mL (1-5 nmol/L)
enhance tumor cell growth in vitro approximately 2- to 3-fold, higher
concentrations, 0.5 to 1 U/mL (5-10 nmol/L) impaired cell growth
approximately 2- to 4-fold. Impaired cell growth was associated with
cell cycle arrest at G2M and increased pre-Go
DNA, as well as apoptosis, measured by tumor cell binding to Annexin
V and propidium iodide. Apoptosis was reversed with the
general caspase inhibitor, FK-011. The enhancing and inhibiting effects
were specific for thrombin (reversed with inactive
diisopropyl-fluorophosphate [DFP]-thrombin) and mediated via the
protease-activated receptor 1 (PAR-1). PAR-1 activation was
demonstrated by (1) use of a cell line, B16F10, devoid of the 3 other
thrombin receptors, PAR-3, PAR-4, and GPIb; and (2) greater sensitivity
of PAR-1 transfected B16F10 and HCT8 cells to impaired cell
growth/apoptosis, 3- and 14-fold, respectively. Thus, thrombin has a
bimodal effect on PAR-1 in tumor cells: enhanced growth at low
concentration, impaired growth/apoptosis at higher concentration.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
N. M. Kuderer, T. L. Ortel, and C. W. Francis
Impact of Venous Thromboembolism and Anticoagulation on Cancer and Cancer Survival
J. Clin. Oncol.,
October 10, 2009;
27(29):
4902 - 4911.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Raivio, R. Lassila, and J. Petaja
Thrombin in myocardial ischemia-reperfusion during cardiac surgery.
Ann. Thorac. Surg.,
July 1, 2009;
88(1):
318 - 325.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Blackburn and C. E. Brinckerhoff
Matrix Metalloproteinase-1 and Thrombin Differentially Activate Gene Expression in Endothelial Cells via PAR-1 and Promote Angiogenesis
Am. J. Pathol.,
December 1, 2008;
173(6):
1736 - 1746.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Hu, J. M. Roth, P. Brooks, J. Luty, and S. Karpatkin
Thrombin Up-regulates Cathepsin D which Enhances Angiogenesis, Growth, and Metastasis
Cancer Res.,
June 15, 2008;
68(12):
4666 - 4673.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Palumbo, K. E. Talmage, J. V. Massari, C. M. La Jeunesse, M. J. Flick, K. W. Kombrinck, Z. Hu, K. A. Barney, and J. L. Degen
Tumor cell-associated tissue factor and circulating hemostatic factors cooperate to increase metastatic potential through natural killer cell-dependent and-independent mechanisms
Blood,
July 1, 2007;
110(1):
133 - 141.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Goerge, A. Barg, E.-M. Schnaeker, B. Poppelmann, V. Shpacovitch, A. Rattenholl, C. Maaser, T. A. Luger, M. Steinhoff, and S. W. Schneider
Tumor-derived matrix metalloproteinase-1 targets endothelial proteinase-activated receptor 1 promoting endothelial cell activation.
Cancer Res.,
August 1, 2006;
66(15):
7766 - 7774.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Zania, S. Kritikou, C. S. Flordellis, M. E. Maragoudakis, and N. E. Tsopanoglou
Blockade of Angiogenesis by Small Molecule Antagonists to Protease-Activated Receptor-1: Association with Endothelial Cell Growth Suppression and Induction of Apoptosis
J. Pharmacol. Exp. Ther.,
July 1, 2006;
318(1):
246 - 254.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Caunt, L. Hu, T. Tang, P. C. Brooks, S. Ibrahim, and S. Karpatkin
Growth-regulated oncogene is pivotal in thrombin-induced angiogenesis.
Cancer Res.,
April 15, 2006;
66(8):
4125 - 4132.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Swift, A. J. Leger, J. Talavera, L. Zhang, A. Bohm, and A. Kuliopulos
Role of the PAR1 Receptor 8th Helix in Signaling: THE 7-8-1 RECEPTOR ACTIVATION MECHANISM
J. Biol. Chem.,
February 17, 2006;
281(7):
4109 - 4116.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Feistritzer and M. Riewald
Endothelial barrier protection by activated protein C through PAR1-dependent sphingosine 1-phosphate receptor-1 crossactivation
Blood,
April 15, 2005;
105(8):
3178 - 3184.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Zhang, J. L. Hunt, D. P. Landsittel, S. Muller, K. Adler-Storthz, R. L. Ferris, D. M. Shin, and Z.(G. Chen
Correlation of Protease-Activated Receptor-1 With Differentiation Markers in Squamous Cell Carcinoma of the Head and Neck and Its Implication in Lymph Node Metastasis
Clin. Cancer Res.,
December 15, 2004;
10(24):
8451 - 8459.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Hu, M. Lee, W. Campbell, R. Perez-Soler, and S. Karpatkin
Role of endogenous thrombin in tumor implantation, seeding, and spontaneous metastasis
Blood,
November 1, 2004;
104(9):
2746 - 2751.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Dorfleutner, E. Hintermann, T. Tarui, Y. Takada, and W. Ruf
Cross-talk of Integrin {alpha}3{beta}1 and Tissue Factor in Cell Migration
Mol. Biol. Cell,
October 1, 2004;
15(10):
4416 - 4425.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Shi, B. Gangadharan, L. F. Brass, W. Ruf, and B. M. Mueller
Protease-Activated Receptors (PAR1 and PAR2) Contribute to Tumor Cell Motility and Metastasis
Mol. Cancer Res.,
July 1, 2004;
2(7):
395 - 402.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. C. Chin, N. Vergnolle, W. K. MacNaughton, J. L. Wallace, M. D. Hollenberg, and A. G. Buret
Proteinase-activated receptor 1 activation induces epithelial apoptosis and increases intestinal permeability
PNAS,
September 16, 2003;
100(19):
11104 - 11109.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. B. Sorensen, L. V. M. Rao, D. Tornehave, S. Gammeltoft, and L. C. Petersen
Antiapoptotic effect of coagulation factor VIIa
Blood,
September 1, 2003;
102(5):
1708 - 1715.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Fang, K. J Kovacs, L. L Fisher, and A. A Larson
Thrombin inhibits NMDA-mediated nociceptive activity in the mouse: possible mediation by endothelin
J. Physiol.,
June 15, 2003;
549(3):
903 - 917.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. E. Tsopanoglou, P. Andriopoulou, and M. E. Maragoudakis
On the mechanism of thrombin-induced angiogenesis: involvement of alpha vbeta 3-integrin
Am J Physiol Cell Physiol,
November 1, 2002;
283(5):
C1501 - C1510.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Kamath, A. Meydani, F. Foss, and A. Kuliopulos
Signaling from Protease-activated Receptor-1 Inhibits Migration and Invasion of Breast Cancer Cells
Cancer Res.,
August 1, 2001;
61(15):
5933 - 5940.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Ahmad, J. Menezes, and A. Ahmad
Signaling mechanism in the induction of apoptosis by thrombin in human tumor cells
Blood,
December 1, 2000;
96(12):
4001 - 4002.
[Full Text]
[PDF]
|
|
|
|
|
