| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Tumor Biology |
Experimental Therapeutics Division, Ontario Cancer Institute/Princess Margaret Hospital [R. A. C., T. K., R. P. H.] and Departments of Medical Biophysics [R. A. C., T. K., R. P. H.] and Radiation Oncology [R. P. H.], University of Toronto, Toronto, Ontario, M5G 2M9 Canada
Hypoxia exists in most human and rodent solid tumors and has been shown to correlate with poor survival in carcinoma of the cervix, carcinoma of the head and neck, and soft tissue sarcoma. It exists both chronically, due to the poorly organized vasculature of solid tumors, and acutely, due to fluctuations in blood flow. It has been found that tumors that are more hypoxic are more likely to metastasize in humans and in rodent models, and it has been demonstrated that exposure of tumor cells to hypoxia in vitro can transiently enhance their metastatic potential when they are reinjected i.v. into mice. The purpose of the present study was to determine whether experimentally imposed hypoxic stress in vivo, either chronic or acute, affects the process of spontaneous metastasis in tumor-bearing mice. We exposed mice bearing KHT tumors to low oxygen conditions (5–7% O2 breathing) daily during tumor growth in an attempt to induce additional chronic (2 h/day) and acute (12 x 10 min/day) hypoxia in their tumors. By monitoring tumor pO2 levels over the course of treatment, we demonstrated that these treatments produce acute and chronic hypoxia within the tumor tissue. The acute but not the chronic hypoxia treatment significantly increased the number of spontaneous microscopic lung metastases in the mice by a factor of about 2, and the results suggest that this effect was due to the changes induced in the primary tumor. This study describes a novel method for studying the effects of hypoxia in solid tumors and demonstrates that acute and chronic hypoxia can have different effects on tumor cell behavior in vivo.
This article has been cited by other articles:
|
|
 |
|
  C.A. Stein, S. Wu, A. M. Voskresenskiy, J.-F. Zhou, J. Shin, P. Miller, N. Souleimanian, and L. Benimetskaya G3139, an Anti-Bcl-2 Antisense Oligomer That Binds Heparin-Binding Growth Factors and Collagen I, Alters In vitro Endothelial Cell Growth and Tubular Morphogenesis Clin. Cancer Res., April 15, 2009; 15(8): 2797 - 2807. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Monnier, P. Farmer, G. Bieler, N. Imaizumi, T. Sengstag, G. C. Alghisi, J.-C. Stehle, L. Ciarloni, S. Andrejevic-Blant, R. Moeckli, et al. CYR61 and {alpha}V{beta}5 Integrin Cooperate to Promote Invasion and Metastasis of Tumors Growing in Preirradiated Stroma Cancer Res., September 15, 2008; 68(18): 7323 - 7331. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. I. Cardenas-Navia, D. Mace, R. A. Richardson, D. F. Wilson, S. Shan, and M. W. Dewhirst The Pervasive Presence of Fluctuating Oxygenation in Tumors Cancer Res., July 15, 2008; 68(14): 5812 - 5819. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mayer, M. Hockel, A. Wree, C. Leo, L.-C. Horn, and P. Vaupel Lack of Hypoxic Response in Uterine Leiomyomas despite Severe Tissue Hypoxia Cancer Res., June 15, 2008; 68(12): 4719 - 4726. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Vaupel Hypoxia and Aggressive Tumor Phenotype: Implications for Therapy and Prognosis Oncologist, May 1, 2008; 13(suppl_3): 21 - 26. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. R Wilson, K. O Hicks, F. B Pruijn, and A. V Patterson Targeting Tumor Hypoxia with Prodrugs: Challenges and Opportunities Am. Assoc. Cancer Res. Educ. Book, April 12, 2008; 2008(1): 293 - 310. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Supiot, R. P. Hill, and R. G. Bristow Nutlin-3 radiosensitizes hypoxic prostate cancer cells independent of p53 Mol. Cancer Ther., April 1, 2008; 7(4): 993 - 999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Wouters, B. Pauwels, F. Lardon, and J. B. Vermorken Review: Implications of In Vitro Research on the Effect of Radiotherapy and Chemotherapy Under Hypoxic Conditions Oncologist, June 1, 2007; 12(6): 690 - 712. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Chaudary and R. P. Hill Hypoxia and Metastasis Clin. Cancer Res., April 1, 2007; 13(7): 1947 - 1949. [Full Text] [PDF]
|
|
|
|
|
|
E. K. Rofstad, K. Galappathi, B. Mathiesen, and E.-B. M. Ruud Fluctuating and Diffusion-Limited Hypoxia in Hypoxia-Induced Metastasis Clin. Cancer Res., April 1, 2007; 13(7): 1971 - 1978. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Martinive, F. Defresne, C. Bouzin, J. Saliez, F. Lair, V. Gregoire, C. Michiels, C. Dessy, and O. Feron Preconditioning of the Tumor Vasculature and Tumor Cells by Intermittent Hypoxia: Implications for Anticancer Therapies Cancer Res., December 15, 2006; 66(24): 11736 - 11744. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. K. Rofstad, B. Mathiesen, K. Kindem, and K. Galappathi Acidic Extracellular pH Promotes Experimental Metastasis of Human Melanoma Cells in Athymic Nude Mice. Cancer Res., July 1, 2006; 66(13): 6699 - 6707. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. B. Frieboes, X. Zheng, C.-H. Sun, B. Tromberg, R. Gatenby, and V. Cristini An Integrated Computational/Experimental Model of Tumor Invasion Cancer Res., February 1, 2006; 66(3): 1597 - 1604. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Koshikawa and K. Takenaga Hypoxia-Regulated Expression of Attenuated Diphtheria Toxin A Fused with Hypoxia-Inducible Factor-1{alpha} Oxygen-Dependent Degradation Domain Preferentially Induces Apoptosis of Hypoxic Cells in Solid Tumor Cancer Res., December 15, 2005; 65(24): 11622 - 11630. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Cristini, H. B. Frieboes, R. Gatenby, S. Caserta, M. Ferrari, and J. Sinek Morphologic Instability and Cancer Invasion Clin. Cancer Res., October 1, 2005; 11(19): 6772 - 6779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. K. Rofstad, B. Mathiesen, K. Henriksen, K. Kindem, and K. Galappathi The Tumor Bed Effect: Increased Metastatic Dissemination from Hypoxia-Induced Up-regulation of Metastasis-Promoting Gene Products Cancer Res., March 15, 2005; 65(6): 2387 - 2396. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Vaupel The Role of Hypoxia-Induced Factors in Tumor Progression Oncologist, November 1, 2004; 9(suppl_5): 10 - 17. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. I. Cardenas-Navia, D. Yu, R. D. Braun, D. M. Brizel, T. W. Secomb, and M. W. Dewhirst Tumor-dependent Kinetics of Partial Pressure of Oxygen Fluctuations during Air and Oxygen Breathing Cancer Res., September 1, 2004; 64(17): 6010 - 6017. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Maseide, R. A. Kandel, R. S. Bell, C. N. Catton, B. O'Sullivan, J. S. Wunder, M. Pintilie, D. Hedley, and R. P. Hill Carbonic Anhydrase IX as a Marker for Poor Prognosis in Soft Tissue Sarcoma Clin. Cancer Res., July 1, 2004; 10(13): 4464 - 4471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Cairns and R. P. Hill Acute Hypoxia Enhances Spontaneous Lymph Node Metastasis in an Orthotopic Murine Model of Human Cervical Carcinoma Cancer Res., March 15, 2004; 64(6): 2054 - 2061. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Hedley, M. Pintilie, J. Woo, T. Nicklee, A. Morrison, D. Birle, A. Fyles, M. Milosevic, and R. Hill Up-Regulation of the Redox Mediators Thioredoxin and Apurinic/Apyrimidinic Excision (APE)/Ref-1 in Hypoxic Microregions of Invasive Cervical Carcinomas, Mapped Using Multispectral, Wide-Field Fluorescence Image Analysis Am. J. Pathol., February 1, 2004; 164(2): 557 - 565. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. K. Rofstad, B. Mathiesen, and K. Galappathi Increased Metastatic Dissemination in Human Melanoma Xenografts after Subcurative Radiation Treatment: Radiation-induced Increase in Fraction of Hypoxic Cells and Hypoxia-induced Up-Regulation of Urokinase-Type Plasminogen Activator Receptor Cancer Res., January 1, 2004; 64(1): 13 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N Raghunand, R A Gatenby, and R J Gillies Microenvironmental and cellular consequences of altered blood flow in tumours Br. J. Radiol., December 1, 2003; 76(suppl_1): S11 - S22. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-M. Postovit, M. A. Adams, G. E. Lash, J. P. Heaton, and C. H. Graham Oxygen-mediated Regulation of Tumor Cell Invasiveness. INVOLVEMENT OF A NITRIC OXIDE SIGNALING PATHWAY J. Biol. Chem., September 13, 2002; 277(38): 35730 - 35737. [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 |
