geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Angiogenesis and tumor growth inhibition by a matrix metalloproteinase inhibitor targeting radiation-induced invasion


, : Angiogenesis and tumor growth inhibition by a matrix metalloproteinase inhibitor targeting radiation-induced invasion. Molecular Cancer Therapeutics 4(11): 1717-1728

In this study, we have evaluated the interactions between ionizing radiation and a matrix metalloproteinase (MMP) inhibitor. Using Matrigel invasion assays, we show that ionizing radiation induced a dose-dependent increase in the invasive phenotype of cultured B16 melanoma cells and that conditioned medium from these irradiated B16 cells promoted enclothelial cell [human microvascular enclothelial cells (HMEC)l invasiveness. To determine whether the radiation-induced changes in invasive phenotype could be due to changes in MMP activation, we have tested the ability of the MMP inhibitor Metastat to modulate the ionizing radiation-induced invasive phenotype using both an in vitro melanoma model and a mouse s.c. tumor model. In these studies, Metastat inhibited the ionizing radiation-induced invasive phenotype in cultured B16 cells and similarly inhibited the increase in HMEC invasion induced by conditioned medium from irradiated B16 cells. Conversely, ionizing radiation increased B16 MMP-2 activity and the conditioned medium from irradiated B16 induced HMEC MMP-2 activity. To further investigate the interaction between ionizing radiation and MMP activation, we then studied the effects of ionizing radiation on downstream effectors of the MMP system. We found that ionizing radiation induced vascular endothelial growth factor (VEGF) secretion by B16 melanoma cells and that this secretion was inhibited by Metastat. Similarly, conditioned medium from irradiated B16 was also able to increase VEGF secretion in HMECs. Moreover, ionizing radiation -induced melanoma cell invasiveness was partially inhibited by an anti-VEGF monoclonal antibody. In vivo, ionizing radiation plus concomitant Metastat yielded the greatest growth inhibition of melanoma s.c. tumors and this effect correlated with inhibition of angiogenesis as measured by both Doppler ultrasonography and platelet/endothelial cell adhesion molecule-1 staining. Finally, ionizing radiation modulated MMP-2, VEGF, and VEGF receptor expression in these tumor samples using immunohistochemistry. Taken together, these results suggest that there is an ionizing radiationinduced tumor survival pathway and a possible paracrine ionizing radiation -induced stimulatory pathway emanating from tumor cells toward the enclothelial bed that is impeded when Metastat is given simultaneously. This model could provide in vivo evidence of the antitumor efficacy of combining a MMP inhibitor with ionizing radiation to target radiation-induced invasion and angiogenesis.

US$19.90

PMID: 16275993

DOI: 10.1158/1535-7163.MCT-05-0179


Other references

Anonymous, 2013: The representation of tool and non-tool object information in the human intraparietal sulcus. Humans have an amazing ability to quickly and efficiently recognize and interact with visual objects in their environment. The underlying neural processes supporting this ability have been mainly explored in the ventral visual stream. However, the...

Zhu Y.; Dong S., 1991: Rapid electrochemical oxidation of hemoglobin at a dye modified electrode. Bioelectrochemistry & Bioenergetics 26(2): 351-357

Kumerova, A.; Lece, A.; Skesters, A.; Silova, A.; Petuhovs, V., 1999: Anaemia and antioxidant defence of the red blood cells. Antioxidant defence was investigated in red blood cells (RBC) in 56 patients with 3 different haemoblastoses: polycythemia vera (PV), chronic myelogenous leukaemia (CML), chronic lymphoid leukemia (CLL) with and without anaemia, in 12 iron deficie...

Bleecker, A.B.; Hall, A.E.; Rodriguez, F.I.; Esch, J.J.; Binder, B., 1999: The ethylene signal transduction pathway. The ethylene signal transduction pathway of Arabidopsis thaliana is summarized, including ethylene receptors, signal transduction, mechanism of ethylene binding and future challenges.

Kuehl, R.O.; Buxton, D.R.; Briggs, R.E., 1976: Application of time series analysis to investigate crop and environment relationships. Percentage boll retention in cotton and 5-day average minimum temperatures were recorded in 1970-2 and investigated to determine whether some aspects of time series analysis could be used to provide valid estimates of correlations between environm...

Rehout, V.; Citek, J.; Kosvanec, K.; Blahova, B.; Hradecka, E., 2004: The application of molecular genetics in the evaluation of variability of cattle. The paper deals with genetic diversity in cattle. As measured by microsatellites and protein loci, the diversity could be restricted in low numbered Red Middleeuropean breeds. Genetic distances among Czech, Polish and German Red breeds were evalua...

Prisinzano, T.; Dukat, Młgorzata.; Law, H.; Slassi, A.; MacLean, N.; DeLannoy, Iés.; Glennon, R.A., 2004: 2-(Anilino)imidazolines and 2-(benzyl)imidazoline derivatives as h5-HT1D serotonin receptor ligands. 2-(Anilino)imidazolines were identified as novel human 5-HT1D receptor ligands, but offered no particular advantage over previously reported 2-(benzyl)imidazolines. Pharmacokinetic and functional data were obtained for selected 2-(benzyl)imidazoli...

Harris, S., Jr., 1939: A simplified high carbohydrate diet in diabetes mellitus. In the author's practice the usual procedure in the management of the mild and the moderately severe diabetic is first to give a 6-hour glucose tolerance test to establish the severity of the disease. The patient is then placed on one of 4 tr...

Ahmad V.U.; Atta U.R.hman; Rasheed T.; Habib U.R.hman, 1987: Jamtine n oxide a new isoquinoline alkaloid from cocculus hirsutus. A new isoquinoline alkaloid, jamtine-N-oxide has been isolated from Cocculus hirsutus. Its structure has been assigned as C20H25NO5 (1) on the basis of spectral studies. Its stereochemistry has been determined by homonuclear 2D 1H-NMR (COSY-45, J-...

Schreier, H.; Erdos, G.; Reimer, K.; König, B.; König, W.; Fleischer, W., 1997: Molecular effects of povidone-iodine on relevant microorganisms: an electron-microscopic and biochemical study. The aim of this study was to elucidate the effects of povidone-iodine (PVP-I) on cell ultrastructure by electron microscopy and to monitor changes in enzyme activity and nucleotide efflux. Staphylococcus aureus, Escherichia coli and Candida albica...