| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Experimental Oncology, Medical Research Council Harwell, Chilton, Didcot OX11 ORD, United Kingdom [L. G., G. U. D., I. J. S.]; Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom [R. B., A. L. H.]; and Department of Pharmacy, University of Manchester, Oxford Road, Manchester M13 9PL, United Kingdom [L. G., I. J. S.]
We report that hypoxia regulates and influences the level of the angiogenic enzyme platelet-derived endothelial cell growth factor (PD-ECGF), also called thymidine phosphorylase, in vitro and in vivo. Levels of PD-ECGF protein increased 6-fold in the breast cancer cell line MDA 231 after 16 h of growth in 0.3% oxygen. A simultaneous increase in enzyme activity was observed. Immunohistochemical staining of MDA 231 tumors grown in nu/nu mice showed increased expression of PD-ECGF in those parts of the tumor that are proximal to the areas of necrosis. In addition, increased and widespread staining for PD-ECGF protein was obtained when the tumor vascular supply was occluded for 2 h by clamping. Lowering the media pH to 6.3–6.7 in vitro also resulted in an increase in PD-ECGF protein levels. This study demonstrates that tumor microenvironmental factors can result in the specific up-regulation of an angiogenic enzyme that can also activate 5-fluorouracil prodrugs and hence is exploitable therapeutically.
1 To whom requests for reprints should be addressed.
Received 11/ 7/96. Accepted 1/ 6/97.
This article has been cited by other articles:
|
|
 |
|
  S. Liekens, A. Bronckaers, A.-I. Hernandez, E.-M. Priego, E. Casanova, M.-J. Camarasa, M.-J. Perez-Perez, and J. Balzarini 5'-O-Tritylated Nucleoside Derivatives: Inhibition of Thymidine Phosphorylase and Angiogenesis Mol. Pharmacol., August 1, 2006; 70(2): 501 - 509. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. H. Slager, M. W. Honders, E. D. van der Meijden, S. A. P. van Luxemburg-Heijs, F. M. Kloosterboer, M. G. D. Kester, I. Jedema, W. A. E. Marijt, M. R. Schaafsma, R. Willemze, et al. Identification of the angiogenic endothelial-cell growth factor-1/thymidine phosphorylase as a potential target for immunotherapy of cancer Blood, June 15, 2006; 107(12): 4954 - 4960. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J-Y Han, E K Hong, S Y Lee, S M Yoon, D H Lee, and J S Lee Thymidine phosphorylase expression in tumour cells and tumour response to capecitabine plus docetaxel chemotherapy in non-small cell lung cancer J. Clin. Pathol., June 1, 2005; 58(6): 650 - 654. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Coward, N. Maisey, and D. Cunningham The effects of capecitabine in Raynaud's disease: a case report Ann. Onc., May 1, 2005; 16(5): 835 - 836. [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Kato, C. A. Lambert, A. C. Colige, P. Mineur, A. Noel, F. Frankenne, J.-M. Foidart, M. Baba, R.-I. Hata, K. Miyazaki, et al. Acidic Extracellular pH Induces Matrix Metalloproteinase-9 Expression in Mouse Metastatic Melanoma Cells through the Phospholipase D-Mitogen-activated Protein Kinase Signaling J. Biol. Chem., March 25, 2005; 280(12): 10938 - 10944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N B Teo, B S Shoker, C Jarvis, J P Sloane, and C Holcombe Thymidine phosphorylase expression and stromal vascularity in ductal carcinoma in situ of the breast J. Clin. Pathol., December 1, 2003; 56(12): 919 - 923. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Stoner, B. Saville, M. Wormke, D. Dean, R. Burghardt, and S. Safe Hypoxia Induces Proteasome-Dependent Degradation of Estrogen Receptor {alpha} in ZR-75 Breast Cancer Cells Mol. Endocrinol., October 1, 2002; 16(10): 2231 - 2242. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Hashimoto, N. Minami, R. Takakura, and H. Imai Bovine Immature Oocytes Acquire Developmental Competence During Meiotic Arrest In Vitro Biol Reprod, June 1, 2002; 66(6): 1696 - 1701. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Frickhofen, F.-J. Beck, B. Jung, H.-G. Fuhr, H. Andrasch, and M. Sigmund Capecitabine can induce acute coronary syndrome similar to 5-fluorouracil Ann. Onc., May 1, 2002; 13(5): 797 - 801. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Uchimiya, T. Furukawa, M. Okamoto, Y. Nakajima, S. Matsushita, R. Ikeda, T. Gotanda, M. Haraguchi, T. Sumizawa, M. Ono, et al. Suppression of Thymidine Phosphorylase-mediated Angiogenesis and Tumor Growth by 2-Deoxy-L-ribose Cancer Res., May 1, 2002; 62(10): 2834 - 2839. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Leek, K. L. Talks, F. Pezzella, H. Turley, L. Campo, N. S. Brown, R. Bicknell, M. Taylor, K. C. Gatter, and A. L. Harris Relation of Hypoxia-inducible Factor-2{alpha} (HIF-2{alpha}) Expression in Tumor-infiltrative Macrophages to Tumor Angiogenesis and the Oxidative Thymidine Phosphorylase Pathway in Human Breast Cancer Cancer Res., March 1, 2002; 62(5): 1326 - 1329. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-i. Aishima, K.-i. Taguchi, K. Sugimachi, Y. Asayama, H. Nishi, M. Shimada, K. Sugimachi, and M. Tsuneyoshi The Role of Thymidine Phosphorylase and Thrombospondin-1 in Angiogenesis and Progression of Intrahepatic Cholangiocarcinoma International Journal of Surgical Pathology, January 1, 2002; 10(1): 47 - 56. [Abstract] [PDF]
|
|
|
|
 |
|
 Y. Yao, T. Kubota, K. Sato, and R. Kitai Macrophage Infiltration-associated Thymidine Phosphorylase Expression Correlates with Increased Microvessel Density and Poor Prognosis in Astrocytic Tumors Clin. Cancer Res., December 1, 2001; 7(12): 4021 - 4026. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. L. West, R. A. Cooper, J. A. Loncaster, D. P. Wilks, and M. Bromley Tumor Vascularity: A Histological Measure of Angiogenesis and Hypoxia Cancer Res., April 1, 2001; 61(7): 2907 - 2910. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. T.-P. Poon, S.-T. Fan, and J. Wong Clinical Implications of Circulating Angiogenic Factors in Cancer Patients J. Clin. Oncol., February 15, 2001; 19(4): 1207 - 1225. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Goto, K. Kohno, S. Sone, S.-i. Akiyama, M. Kuwano, and M. Ono Interferon {{gamma}}-dependent Induction of Thymidine Phosphorylase/Platelet-derived Endothelial Growth Factor through {{gamma}}-Activated Sequence-like Element in Human Macrophages Cancer Res., January 1, 2001; 61(2): 469 - 473. [Abstract] [Full Text]
|
|
|
|
|
|
R. Fujiwaki, K. Hata, K. Nakayama, M. Fukumoto, and K. Miyazaki Gene Expression for Dihydropyrimidine Dehydrogenase and Thymidine Phosphorylase Influences Outcome in Epithelial Ovarian Cancer J. Clin. Oncol., December 1, 2000; 18(23): 3946 - 3951. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. K. Rofstad and E. F. Halsør Vascular Endothelial Growth Factor, Interleukin 8, Platelet-derived Endothelial Cell Growth Factor, and Basic Fibroblast Growth Factor Promote Angiogenesis and Metastasis in Human Melanoma Xenografts Cancer Res., September 1, 2000; 60(17): 4932 - 4938. [Abstract] [Full Text]
|
|
|
|
|
|
E. Sivridis, A. Giatromanolaki, M. I Koukourakis, R. Bicknell, A. L Harris, and K. C Gatter Thymidine phosphorylase expression in normal and hyperplastic endometrium J. Clin. Pathol., September 1, 2000; 53(9): 704 - 708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ueno, M. Toi, H. Saji, M. Muta, H. Bando, K. Kuroi, M. Koike, H. Inadera, and K. Matsushima Significance of Macrophage Chemoattractant Protein-1 in Macrophage Recruitment, Angiogenesis, and Survival in Human Breast Cancer Clin. Cancer Res., August 1, 2000; 6(8): 3282 - 3289. [Abstract] [Full Text]
|
|
|
|
|
|
S. J. Reshkin, A. Bellizzi, V. Albarani, L. Guerra, M. Tommasino, A. Paradiso, and V. Casavola Phosphoinositide 3-Kinase Is Involved in the Tumor-specific Activation of Human Breast Cancer Cell Na+/H+ Exchange, Motility, and Invasion Induced by Serum Deprivation J. Biol. Chem., February 25, 2000; 275(8): 5361 - 5369. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Konda, H. Sato, K. Sakai, M. Sato, S. Orikasa, and N. Kimura Expression of Platelet-Derived Endothelial Cell Growth Factor and its Potential Role in Up-Regulation of Angiogenesis in Scarred Kidneys Secondary to Urinary Tract Diseases Am. J. Pathol., November 1, 1999; 155(5): 1587 - 1597. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Shi, J. L. Abbruzzese, S. Huang, I. J. Fidler, Q. Xiong, and K. Xie Constitutive and Inducible Interleukin 8 Expression by Hypoxia and Acidosis Renders Human Pancreatic Cancer Cells More Tumorigenic and Metastatic Clin. Cancer Res., November 1, 1999; 5(11): 3711 - 3721. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Ignatescu, E. Gharehbaghi-Schnell, A. Hassan, S. Rezaie-Majd, I. Korschineck, R. R. Schleef, H. D. Glogar, and I. M. Lang Expression of the Angiogenic Protein, Platelet-Derived Endothelial Cell Growth Factor, in Coronary Atherosclerotic Plaques : In Vivo Correlation of Lesional Microvessel Density and Constrictive Vascular Remodeling Arterioscler. Thromb. Vasc. Biol., October 1, 1999; 19(10): 2340 - 2347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Toi, T. Ueno, H. Matsumoto, H. Saji, N. Funata, M. Koike, and T. Tominaga Significance of Thymidine Phosphorylase as a Marker of Protumor Monocytes in Breast Cancer Clin. Cancer Res., May 1, 1999; 5(5): 1131 - 1137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Matsushita, T. Nitanda, T. Furukawa, T. Sumizawa, A. Tani, K. Nishimoto, S. Akiba, K. Miyadera, M. Fukushima, Y. Yamada, et al. The Effect of a Thymidine Phosphorylase Inhibitor on Angiogenesis and Apoptosis in Tumors Cancer Res., April 1, 1999; 59(8): 1911 - 1916. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
