Cited by 327Cancer, Hypoxia, and MetabolismCancer Cells and MetastasisMechanisms of cancer metastasis

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The hypoxic tumour microenvironment and metastatic progression

Subarsky, Patrick, Hill, Richard P.·2003·Clinical & Experimental Metastasis

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Abstract

The microenvironment of solid tumours contains regions of poor oxygenation and high acidity. Growing evidence from clinical and experimental studies points to a fundamental role for hypoxia in metastatic progression. Prolonged hypoxia increases genomic instability, genomic heterogeneity, and may act as a selective pressure for tumour cell variants. Hypoxia can also act in an epigenetic fashion, altering the expression of genes. Hypoxia-induced changes in gene expression alter non-specific stress responses, anaerobic metabolism, angiogenesis, tissue remodeling, and cell-cell contacts. Experimental studies have demonstrated that inhibition of proteins involved in these processes can modify metastasis formation, suggesting a causal role in metastatic progression. Recent advances in high-throughput screening techniques have allowed identification of many hypoxia-induced genes that are involved in the processes associated with metastasis. Here we review the epigenetic control of gene expression by the hypoxic microenvironment and its potential contribution to metastatic progression.

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Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis
Hanahan, D., & Folkman, J. (1996) · Cell · doi:10.1016/s0092-8674(00)80108-7 · Cited by 6,885
New functions for the matrix metalloproteinases in cancer progression
Egeblad, M., & Werb, Z. (2002) · Nature Reviews Cancer · doi:10.1038/nrc745 · Cited by 6,108
Targeting of HIF-α to the von Hippel-Lindau Ubiquitylation Complex by O 2 -Regulated Prolyl Hydroxylation
Jaakkola, P., Mole, D. R., Tian, Y.-M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A. V., Hebestreit, H. F., Mukherji, M., Schofield, C. J., et al. (2001) · Science · doi:10.1126/science.1059796 · Cited by 5,535
The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Maxwell, P. H., Wiesener, M. S., Chang, G.-W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., & Ratcliffe, P. J. (1999) · Nature · doi:10.1038/20459 · Cited by 5,180
How Matrix Metalloproteinases Regulate Cell Behavior
Sternlicht, M. D., & Werb, Z. (2001) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.17.1.463 · Cited by 3,959
Disruption of epithelial cell-matrix interactions induces apoptosis
Frisch, S., & Francis, H. (1994) · The Journal of Cell Biology · doi:10.1083/jcb.124.4.619 · Cited by 3,276
A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation
Semenza, G. L., & Wang, G. L. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.12.5447 · Cited by 2,617
Cellular and developmental control of O 2 homeostasis by hypoxia-inducible factor 1α
Iyer, N. V., Kotch, L. E., Agani, F., Leung, S. W., Laughner, E., Wenger, R. H., Gassmann, M., Gearhart, J. D., Lawler, A. M., Yu, A. Y., et al. (1998) · Genes & Development · doi:10.1101/gad.12.2.149 · Cited by 2,476
Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours
Graeber, T. G., Osmanian, C., Jacks, T., Housman, D. E., Koch, C. J., Lowe, S. W., & Giaccia, A. J. (1996) · Nature · doi:10.1038/379088a0 · Cited by 2,300
The Histological Structure of Some Human Lung Cancers and the Possible Implications for Radiotherapy
Thomlinson, R. H., & Gray, L. H. (1955) · British Journal of Cancer · doi:10.1038/bjc.1955.55 · Cited by 2,228
Untitled work
(1999) · PubMed · Cited by 2,204
Interleukin-8 as a macrophage-derived mediator of angiogenesis
Koch, A. E., Polverini, P. J., Kunkel, S. L., Harlow, L. A., DiPietro, L. A., Elner, V. M., Elner, S. G., & Strieter, R. M. (1992) · Science · doi:10.1126/science.1281554 · Cited by 2,135
Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix.
Höckel, M., Schlenger, K., Aral, B., Mitze, M., Schäffer, U., & Vaupel, P. W. (1996) · PubMed · Cited by 1,727
Asparagine Hydroxylation of the HIF Transactivation Domain: A Hypoxic Switch
Lando, D., Peet, D. J., Whelan, D. A., Gorman, J. J., & Whitelaw, M. L. (2002) · Science · doi:10.1126/science.1068592 · Cited by 1,558
Untitled work
(2000) · PubMed · Cited by 1,445
HER2 (neu) Signaling Increases the Rate of Hypoxia-Inducible Factor 1α (HIF-1α) Synthesis: Novel Mechanism for HIF-1-Mediated Vascular Endothelial Growth Factor Expression
Laughner, E., Taghavi, P., Chiles, K., Mahon, P. C., & Semenza, G. L. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.12.3995-4004.2001 · Cited by 1,256 · cited 1×
“Growth factor stimulation of HIF-1α protein synthesis can also occur, mediated through receptor tyrosine kinase signal transduction converging through the PI3K/PKBAKT pathway [49, 50].”
Background
Multistep Nature of Metastatic Inefficiency
Luzzi, K. J., MacDonald, I. C., Schmidt, E. E., Kerkvliet, N. I., Morris, V. L., Chambers, A. F., & Groom, A. C. (1998) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65628-3 · Cited by 1,246
Untitled work
(1996) · PubMed · Cited by 1,188
The implications of angiogenesis for the biology and therapy of cancer metastasis
Fidler, I. J. (1994) · Cell · doi:10.1016/0092-8674(94)90187-2 · Cited by 1,099
Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth
Maxwell, P. H., Dachs, G. U., Gleadle, J. M., Nicholls, L. G., Harris, A. L., Stratford, I. J., Hankinson, O., Pugh, C. W., & Ratcliffe, P. J. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.15.8104 · Cited by 1,084
Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness
Birchmeier, W., & Behrens, J. (1994) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/0304-419x(94)90003-5 · Cited by 1,021
Independent function of two destruction domains in hypoxia-inducible factor-α chains activated by prolyl hydroxylation
Masson, N., Willam, C., Maxwell, P. H., Pugh, C. W., & Ratcliffe, P. J. (2001) · The EMBO Journal · doi:10.1093/emboj/20.18.5197 · Cited by 1,014 · cited 1×
“Recent studies have shown that hypoxia leads to decreased proteosomal degradation of HIF-1α due to the lack of prolyl hydroxylation of residues within the oxygen-dependent degradation domain, resulting in the inability of VHL to bind [46, 47].”
Background
Clinical applications of angiogenic growth factors and their inhibitors
Ferrara, N., & Alitalo, K. (1999) · Nature Medicine · doi:10.1038/70928 · Cited by 1,004
The plasminogen activation system in tumor growth, invasion, and metastasis
Andreasen, P. A., Egelund, R., & Petersen, H. H. (2000) · Cellular and Molecular Life Sciences · doi:10.1007/s000180050497 · Cited by 947
Pretreatment oxygenation predicts radiation response in advanced squamous cell carcinoma of the head and neck
Nordsmark, M., Overgaard, M., & Overgaard, J. (1996) · Radiotherapy and Oncology · doi:10.1016/s0167-8140(96)91811-3 · Cited by 942
Hypoxia-inducible factor 1: oxygen homeostasis and disease pathophysiology
Semenza, G. L. (2001) · Trends in Molecular Medicine · doi:10.1016/s1471-4914(01)02090-1 · Cited by 930
Identifying differences in mRNA expression by representational difference analysis of cDNA
Hubank, M. J. F., & Schatz, D. G. (1994) · Nucleic Acids Research · doi:10.1093/nar/22.25.5640 · Cited by 873
High lactate levels predict likelihood of metastases, tumor recurrence, and restricted patient survival in human cervical cancers.
Walenta, S., Wetterling, M., Lehrke, M., Schwickert, G., Sundfør, K., Rofstad, E. K., & Mueller‐Klieser, W. (2000) · PubMed · Cited by 817
Vascular Permeability Factor/Vascular Endothelial Growth Factor and the Significance of Microvascular Hyperpermeability in Angiogenesis
Dvorak, H. F., Nagy, J. A., Feng, D., Brown, L. F., & Dvorak, A. M. (1999) · Current Topics in Microbiology and Immunology · doi:10.1007/978-3-642-59953-8_6 · Cited by 743
Regulation of angiogenesis via vascular endothelial growth factor receptors.
Veikkola, T., Karkkainen, M. J., Claesson, L., & Alitalo, K. K. (2000) · PubMed · Cited by 740
Regulation of Integrin Function by the Urokinase Receptor
Wei, Y., Lukashev, M., Simon, D. I., Bodary, S. C., Rosenberg, S., DOYLE, M. V., & Chapman, H. A. (1996) · Science · doi:10.1126/science.273.5281.1551 · Cited by 727
Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: a new model for metastasis
Al‐Mehdi, A., Tozawa, K., Fisher, A. B., Shientag, L., Lee, A., & Muschel, R. J. (2000) · Nature Medicine · doi:10.1038/71429 · Cited by 703
The biology of cell locomotion within three-dimensional extracellular matrix
Friedl, P., & Br�cker, E.-B. (2000) · Cellular and Molecular Life Sciences · doi:10.1007/s000180050498 · Cited by 651
General mechanisms of metastasis
Woodhouse, E. C., Chuaqui, R. F., & Liotta, L. A. (1997) · Cancer · doi:10.1002/(sici)1097-0142(19971015)80:8+ · Cited by 621
Hypoxia Induces Accumulation of p53 Protein, but Activation of a G 1 -Phase Checkpoint by Low-Oxygen Conditions Is Independent of p53 Status
Graeber, T. G., Peterson, J., Tsai, M., Monica, K., Fornace, A. J., & Giaccia, A. J. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.9.6264 · Cited by 617
Untitled work
(2000) · PubMed · Cited by 614
Untitled work
(2001) · PubMed · Cited by 605
Oxygenation of head and neck cancer: changes during radiotherapy and impact on treatment outcome
Brizel, D. M., Dodge, R. K., Clough, R. W., & Dewhirst, M. W. (1999) · Radiotherapy and Oncology · doi:10.1016/s0167-8140(99)00102-4 · Cited by 548
Carbonic anhydrase (CA IX) expression, a potential new intrinsic marker of hypoxia: correlations with tumor oxygen measurements and prognosis in locally advanced carcinoma of the cervix.
Loncaster, J. A., Harris, A. L., Davidson, S. E., Logue, J. P., Hunter, R. D., Wycoff, C. C., Pastorek, J., Ratcliffe, P. J., Stratford, I. J., & West, C. (2001) · PubMed · Cited by 482
Demographic variations in the rising incidence of esophageal adenocarcinoma in white males
Bollschweiler, E., Wolfgarten, E., Gutschow, C. A., & H�lscher, A. H. (2001) · Cancer · doi:10.1002/1097-0142(20010801)92:3 · Cited by 452
Hypoxia causes the activation of nuclear factor kappa B through the phosphorylation of I kappa B alpha on tyrosine residues.
Koong, A. C., Chen, E. Y., & Giaccia, A. J. (1994) · PubMed · Cited by 445
23 Genetic instability induced by the tumor microenvironment
Glazer, P. M., Reynolds, T. Y., & Rockwell, S. (1997) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/s0360-3016(97)80581-0 · Cited by 429
Modification of hypoxia-induced radioresistance in tumors by the use of oxygen and sensitizers
Overgaard, J., & Horsman, M. R. (1996) · Seminars in Radiation Oncology · doi:10.1016/s1053-4296(96)80032-4 · Cited by 420
Osteopontin Identified as Lead Marker of Colon Cancer Progression, Using Pooled Sample Expression Profiling
Agrawal, D. (2002) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/94.7.513 · Cited by 413
IL-8 produced by human malignant melanoma cells in vitro is an essential autocrine growth factor.
Schadendorf, D., Möller, A., Algermissen, B., Worm, M., Sticherling, M., & Czarnetzki, B. M. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.5.2667 · Cited by 412
Tumor Hypoxia Has Independent Predictor Impact Only in Patients With Node-Negative Cervix Cancer
Fyles, A., Milosevic, M., Hedley, D., Pintilie, M., Levin, W., Manchul, L., & Hill, R. P. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.20.3.680 · Cited by 398
Thymidine phosphorylase is angiogenic and promotes tumor growth.
Moghaddam, A., Zhang, H. T., Fan, T., Hu, D. E., Lees, V. C., Turley, H., Fox, S. B., Gatter, K. C., Harris, A. L., & Bicknell, R. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.4.998 · Cited by 390
Hypoxia induces DNA overreplication and enhances metastatic potential of murine tumor cells
Young, S. D., Marshall, R. S., & Hill, R. P. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.24.9533 · Cited by 381
‘Angioprevention’: angiogenesis is a common and key target for cancer chemopreventive agents
Tosetti, F., Ferrari, N., Flora, S. D., & Albini, A. (2002) · The FASEB Journal · doi:10.1096/fj.01-0300rev · Cited by 325
Transcriptional Response to Hypoxia in Human Tumors
Lal, A., Peters, H., Croix, B. S., Haroon, Z. A., Dewhirst, M. W., Strausberg, R. L., Kaanders, J. H. A. M., van der Kogel, A. J., & Riggins, G. J. (2001) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/93.17.1337 · Cited by 323
Glucose transporter glut-1 expression correlates with tumor hypoxia and predicts metastasis-free survival in advanced carcinoma of the cervix.
Airley, R. E., Loncaster, J. A., Davidson, S. E., Bromley, M., Roberts, S. K., Patterson, A. V., Hunter, R. D., Stratford, I. J., & West, C. (2001) · PubMed · Cited by 320
Untitled work
(2001) · PubMed · Cited by 292
104 candidate genes for the hypoxic tumor phenotype
Koong, A. C., Denko, N. C., Schindler, C., Le, Q., Terris, D. T., Ibrahim, H. Z., Goffinet, D. R., & Giaccia, A. J. (1999) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/s0360-3016(99)90122-0 · Cited by 290
Metastasis-Suppressor Genes: a Review and Perspective on an Emerging Field
Yoshida, B. A. (2000) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/92.21.1717 · Cited by 273
Blood flow, metabolism, cellular microenvironment, and growth rate of human tumor xenografts.
Kallinowski, F., Schlenger, K., Runkel, S., Kloes, M., Stohrer, M., Okunieff, P., & Vaupel, P. W. (1989) · PubMed · Cited by 269
Tumor cell autocrine motility factor is the neuroleukin/phosphohexose isomerase polypeptide.
Watanabe, H., TAKEHANA, K., Date, M., Shinozaki, T., & Raz, A. (1996) · PubMed · Cited by 268
Identification of novel hypoxia dependent and independent target genes of the von Hippel-Lindau (VHL) tumour suppressor by mRNA differential expression profiling
Wykoff, C. C., Pugh, C. W., Maxwell, P. H., Harris, A. L., & Ratcliffe, P. J. (2000) · Oncogene · doi:10.1038/sj.onc.1204012 · Cited by 267
Steps in tumor metastasis: new concepts from intravital videomicroscopy
Chambers, A. F., MacDonald, I. C., Schmidt, E. E., Koop, S., Morris, V. L., Khokha, R., & Groom, A. C. (1995) · Cancer and Metastasis Reviews · doi:10.1007/bf00690599 · Cited by 265
Influence of the hypoxic subvolume on the survival of patients with head and neck cancer
Stadler, P. F., Becker, A., Feldmann, H. J., Hänsgen, G., Dunst, J., Würschmidt, F., & Molls, M. (1999) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/s0360-3016(99)00115-7 · Cited by 265
Constitutive and inducible interleukin 8 expression by hypoxia and acidosis renders human pancreatic cancer cells more tumorigenic and metastatic.
Shi, Q., Abbruzzese, J. L., Huang, S., Fidler, I. J., Xiong, Q., & Xie, K. (1999) · PubMed · Cited by 261
Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer.
Rudland, P. S., Platt-Higgins, A. M., El‐Tanani, M., Rudland, S. D. S., Barraclough, R., Winstanley, J. H. R., Howitt, R., & West, C. R. (2002) · PubMed · Cited by 258
Hypoxia-associated Induction of Early Growth Response-1 Gene Expression
Yan, S.-F., Lu, J., Zou, Y. S., Soh-Won, J., Cohen, D., Buttrick, P. M., Cooper, D. R., Steinberg, S. F., Mackman, N., Pinsky, D. J., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.21.15030 · Cited by 255
Correlation of high lactate levels in head and neck tumors with incidence of metastasis.
Walenta, S., Salameh, A., Lyng, H., Evensen, J. F., Mitze, M., Rofstad, E. K., & Mueller‐Klieser, W. (1997) · Europe PMC (PubMed Central) · Cited by 251
Carbonic anhydrase IX, an endogenous hypoxia marker, expression in head and neck squamous cell carcinoma and its relationship to hypoxia, necrosis, and microvessel density.
Beasley, N. J. P., Wykoff, C. C., Watson, P. H., Leek, R., Turley, H., Gatter, K. C., Pastorek, J., Cox, G. J., Ratcliffe, P. J., & Harris, A. L. (2001) · PubMed · Cited by 250
Role of Interleukin-8 in Tumor Growth and Metastasis of Human Melanoma
Bar‐Eli, M. (1999) · Pathobiology · doi:10.1159/000028045 · Cited by 248
Activation of AP-1 and of a Nuclear Redox Factor, Ref-1, in the Response of HT29 Colon Cancer Cells to Hypoxia
Yao, K.-S., Xanthoudakis, S., Curran, T., & O'Dwyer, P. J. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.9.5997 · Cited by 241
The integrin-linked kinase (ILK) suppresses anoikis
Attwell, S., Roskelley, C. D., & Dedhar, S. (2000) · Oncogene · doi:10.1038/sj.onc.1203711 · Cited by 239
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.
Rofstad, E. K., & Halsør, E. F. (2000) · PubMed · Cited by 229
Hypoxia in human soft tissue sarcomas: Adverse impact on survival and no association with p53 mutations
Nordsmark, M., Alsner, J., Keller, J. O., Nielsen, O. S., Jensen, O. M., Horsman, M. R., & Overgaard, J. (2001) · British Journal of Cancer · doi:10.1054/bjoc.2001.1728 · Cited by 228
Correlation of high lactate levels in human cervical cancer with incidence of metastasis.
Schwickert, G., Walenta, S., Sundfør, K., Rofstad, E. K., & Mueller-Klieser, W. (1995) · PubMed · Cited by 225
Interleukin 8 expression regulates tumorigenicity and metastasis in human bladder cancer.
Inoue, K., Slaton, J. W., Kim, S. J., Perrotte, P., Eve, B. Y., Bar‐Eli, M., Radinsky, R., & Dinney, C. P. (2000) · PubMed · Cited by 222
Scale-Invariant Behavior and Vascular Network Formation in Normal and Tumor Tissue
Gazit, Y., Berk, D. A., Leunig, M., Baxter, L. T., & Jain, R. K. (1995) · Physical Review Letters · doi:10.1103/physrevlett.75.2428 · Cited by 216
Intratumoral pO2-measurements as predictive assay in the treatment of carcinoma of the uterine cervix
Knocke, T.-H., Weitmann, H.-D., Feldmann, H.-J., Selzer, E., & Pötter, R. (1999) · Radiotherapy and Oncology · doi:10.1016/s0167-8140(99)00139-5 · Cited by 212
The contribution of lactic acid to acidification of tumours: studies of variant cells lacking lactate dehydrogenase
Yamagata, M., Hasuda, K., Stamato, T. D., & Tannock, I. (1998) · British Journal of Cancer · doi:10.1038/bjc.1998.289 · Cited by 211
Carbonic anhydrase 9 as an endogenous marker for hypoxic cells in cervical cancer.
Olive, P. L., Aquino‐Parsons, C., MacPhail, S. H., Liao, S. Y., Raleigh, J. A., Lerman, M. I., & Stanbridge, E. J. (2001) · PubMed · Cited by 208
Hypoxia-regulated carbonic anhydrase-9 (CA9) relates to poor vascularization and resistance of squamous cell head and neck cancer to chemoradiotherapy.
Koukourakis, M. I., Giatromanolaki, A. N., Sivridis, E., Simopoulos, K., Pastorek, J., Wykoff, C. C., Gatter, K. C., & Harris, A. L. (2001) · PubMed · Cited by 200
CD44 is a metastasis suppressor gene for prostatic cancer located on human chromosome 11p13.
Gao, A. C., Lou, W., Dong, J., & Isaacs, J. T. (1997) · PubMed · Cited by 197
Studies with glycolysis-deficient cells suggest that production of lactic acid is not the only cause of tumor acidity.
Newell, K. J., Franchi, A. J., Pouysségur, J., & Tannock, I. F. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.3.1127 · Cited by 196
Autotaxin (NPP-2), a metastasis-enhancing motogen, is an angiogenic factor.
Nam, S. W., Clair, T., Kim, Y. S., McMarlin, A., Schiffmann, E., Liotta, L. A., & Stracke, M. L. (2001) · PubMed · Cited by 195
Hypoxia-induced treatment failure in advanced squamous cell carcinoma of the uterine cervix is primarily due to hypoxia-induced radiation resistance rather than hypoxia-induced metastasis
Rofstad, E. K., Sundfør, K., Lyng, H., & Tropé, C. (2000) · British Journal of Cancer · doi:10.1054/bjoc.2000.1266 · Cited by 194
Physical and Functional Sensitivity of Zinc Finger Transcription Factors to Redox Change
Wu, X., Bishopric, N. H., Discher, D. J., Murphy, B. J., & Webster, K. A. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.3.1035 · Cited by 192
Fibroblast growth factors: at the heart of angiogenesis.
Slavin, J. P. (1995) · Cell Biology International · doi:10.1006/cbir.1995.1087 · Cited by 187
Hypoxia Stimulates Urokinase Receptor Expression Through a Heme Protein-Dependent Pathway
Graham, C. H., Fitzpatrick, T. E., & McCrae, K. R. (1998) · Blood · doi:10.1182/blood.v91.9.3300 · Cited by 184
The influence of oxygen tension and pH on the expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase in human breast tumor cells grown in vitro and in vivo.
Griffiths, L. A., Dachs, G. U., Bicknell, R., Harris, A. L., & Stratford, I. J. (1997) · PubMed · Cited by 175
Substrate balances across colonic carcinomas in humans.
Holm, E., Hagmüller, E., Staedt, U., Schlickeiser, G., Günther, H.-J., Leweling, H., TOKUS, M., & Kollmar, H. B. (1995) · PubMed · Cited by 168
Hypoxia Regulates β-Enolase and Pyruvate Kinase-M Promoters by Modulating Sp1/Sp3 Binding to a Conserved GC Element
Discher, D. J., Bishopric, N. H., Wu, X., Peterson, C. A., & Webster, K. A. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.40.26087 · Cited by 166
Hypoxia-induced up-regulation of angiogenin in human malignant melanoma.
Hartmann, A., Kunz, M., Köstlin, S., Gillitzer, R., Toksoy, A., Bröcker, E. B., & Klein, C. E. (1999) · PubMed · Cited by 160
Hypoxia promotes lymph node metastasis in human melanoma xenografts by up-regulating the urokinase-type plasminogen activator receptor.
Rofstad, E. K., Rasmussen, H., Galappathi, K., Mathiesen, B. S., Nilsen, K., & Graff, B. A. (2002) · PubMed · Cited by 160
Molecular Characterization of the Novel Basic Helix–Loop–Helix Protein DEC1 Expressed in Differentiated Human Embryo Chondrocytes
Shen, M., Kawamoto, T., Yan, W., Nakamasu, K., Tamagami, M., Koyano, Y., Noshiro, M., & Kato, Y. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.6960 · Cited by 155
Concepts of oxygen transport at the microcirculatory level
Dewhirst, M. W. (1998) · Seminars in Radiation Oncology · doi:10.1016/s1053-4296(98)80040-4 · Cited by 155
Identification of a tightly regulated hypoxia-response element in the promoter of human plasminogen activator inhibitor–1
Fink, T., Kazlauskas, A., Poellinger, L., Ebbesen, P., & Zachar, V. (2002) · Blood · doi:10.1182/blood.v99.6.2077 · Cited by 152
Epigenetic regulation of gene expression in cervical cancer cells by the tumor microenvironment.
Denko, N. C., Schindler, C., Koong, A. C., Laderoute, K. R., Green, C., & Giaccia, A. J. (2000) · PubMed · Cited by 148
Cytokine-induced pseudopodial protrusion is coupled to tumour cell migration
Guirguis, R., Margulies, I., Taraboletti, G., Schiffmann, E., & Liotta, L. A. (1987) · Nature · doi:10.1038/329261a0 · Cited by 145
Expression and growth-promoting function of the IL-8 receptor β in human melanoma cells
Norgauer, J., Metzner, B., & Schraufstätter, I. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.156.3.1132 · Cited by 144
Molecular basis of hypoxia-induced erythropoietin expression
Wang, G. L., & Semenza, G. L. (1996) · Current Opinion in Hematology · doi:10.1097/00062752-199603020-00009 · Cited by 131
Hypoxia-induced metastasis of human melanoma cells: involvement of vascular endothelial growth factor-mediated angiogenesis
Rofstad, E. K., & Danielsen, T. (1999) · British Journal of Cancer · doi:10.1038/sj.bjc.6690586 · Cited by 130
Nicotinamide and Other Benzamide Analogs as Agents for Overcoming Hypoxic Cell Radiation Resistance in Tumours
Horsman, M. R. (1995) · Acta Oncologica · doi:10.3109/02841869509094031 · Cited by 126
[19] cDNA representational difference analysis: A sensitive and flexible method for identification of differentially expressed genes
Hubank, M. J. F., & Schatz, D. G. (1999) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(99)03021-9 · Cited by 125
Effects of Reoxygenation on Cells From Hypoxic Regions of Solid Tumors: Anticancer Drug Sensitivity and Metastatic Potential
Young, S. D., & Hill, R. P. (1990) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/82.5.371 · Cited by 125
The hypoxia-inducible genes VEGF and CA9 are differentially regulated in superficial vs invasive bladder cancer
TURNER, K. J., CREW, J. P., Wykoff, C. C., Watson, P. H., Poulsom, R., Pastorek, J., Ratcliffe, P. J., Cranston, D., & Harris, A. L. (2002) · British Journal of Cancer · doi:10.1038/sj.bjc.6600215 · Cited by 122
Mammary epithelial-specific expression of the integrin linked kinase (ILK) results in the induction of mammary gland hyperplasias and tumors in transgenic mice
White, D. E., Cardiff, R. D., Dedhar, S., & Muller, W. J. (2001) · Oncogene · doi:10.1038/sj.onc.1204910 · Cited by 120
Inhibition of Growth and Metastasis of Human Pancreatic Cancer Growing in Nude Mice by PTK 787/ZK222584, an Inhibitor of the Vascular Endothelial Growth Factor Receptor Tyrosine Kinases
Solórzano, C. C., Baker, C. H., Bruns, C. J., Killion, J. J., Ellis, L. M., Wood, J. M., & Fidler, I. J. (2001) · Cancer Biotherapy and Radiopharmaceuticals · doi:10.1089/108497801753354267 · Cited by 118
Anoikis and metastatic potential of cloudman S91 melanoma cells.
Zhu, Z., Sanchez-Sweatman, O. H., Huang, X., Wiltrout, R. H., Khokha, R., Zhao, Q., & Gorelik, E. (2001) · PubMed · Cited by 114
Pulmonary and lymph node metastasis is associated with primary tumor interstitial fluid pressure in human melanoma xenografts.
Rofstad, E. K., Tunheim, S. H., Mathiesen, B. S., Graff, B. A., Halsør, E. F., Nilsen, K., & Galappathi, K. (2002) · PubMed · Cited by 106
Treatment outcome in advanced squamous cell carcinoma of the uterine cervix: relationships to pretreatment tumor oxygenation and vascularization
Sundfør, K., Lyng, H., Tropé, C., & Rofstad, E. K. (2000) · Radiotherapy and Oncology · doi:10.1016/s0167-8140(99)00175-9 · Cited by 103
Cooperation Between Transcription Factor AP-1 and NF-kappa B in the Induction of Interleukin-8 in Human Pancreatic Adenocarcinoma Cells by Hypoxia
Shi, Q., Le, X., Abbruzzese, J. L., Wang, B., Mujaida, N., Matsushima, K., Huang, S., Xiong, Q., & Xie, K. (1999) · Journal of Interferon & Cytokine Research · doi:10.1089/107999099312821 · Cited by 101
Anoxia-Induced Up-Regulation of Interleukin-8 in Human Malignant Melanoma
Kunz, M., Hartmann, A., Flory, E., Toksoy, A., Koczan, D., Thiesen, H., Mukaida, N., Neumann, M., Rapp, U. R., Bröcker, E., et al. (1999) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65174-7 · Cited by 98
Relationship of hypoxia to metastatic ability in rodent tumours
Jaeger, K. D., Kavanagh, M.-C., & Hill, R. P. (2001) · British Journal of Cancer · doi:10.1054/bjoc.2001.1743 · Cited by 90
Repeatability and prognostic impact of the pretreatment pO2 histography in patients with advanced head and neck cancer
Rudat, V., Vanselow, B., Wollensack, P., Bettscheider, C., Osman-Ahmet, S., Eble, M. J., & Dietz, A. (2000) · Radiotherapy and Oncology · doi:10.1016/s0167-8140(00)00200-0 · Cited by 86
Oxygen-Mediated Regulation of Gelatinase and Tissue Inhibitor of Metalloproteinases-1 Expression by Invasive Cells
Canning, M. T., Postovit, L.-M. M., Clarke, S. H., & Graham, C. H. (2001) · Experimental Cell Research · doi:10.1006/excr.2001.5243 · Cited by 83
Growth inhibition of human pancreatic cancer cell lines by anti-sense oligonucleotides specific to mutated K-ras genes
Kita, K., Saito, S., Morioka, C. Y., & Watanabe, A. (1999) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19990209)80:4 · Cited by 82
Identification of Genes Differentially Induced by Hypoxia in Pancreatic Cancer Cells
Yoon, D. Y., Büchler, P., Saarikoski, S. T., Hines, O. J., Reber, H. A., & Hankinson, O. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.5867 · Cited by 81
Hypoxia-associated spontaneous pulmonary metastasis in human melanoma xenografts: involvement of microvascular hot spots induced in hypoxic foci by interleukin 8
Rofstad, E. K., & Halsør, E. F. (2002) · British Journal of Cancer · doi:10.1038/sj.bjc.6600052 · Cited by 78
Nuclear Factor Interleukin 6 Motifs Mediate Tissue-specific Gene Transcription in Hypoxia
Yan, S., Zou, Y. S., Mendelsohn, M. M., Gao, Y. J., Naka, Y., Yan, S. D., Pinsky, D. J., & Stern, D. M. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.7.4287 · Cited by 77
Level of interleukin-8 expression by metastatic human melanoma cells directly correlates with constitutive NF-κB activity
Huang, S., DeGuzman, A., Bucana, C. D., & Fidler, I. J. (2000) · Cytokines Cellular & Molecular Therapy · doi:10.1080/13684730050515868 · Cited by 75
Why Are Cancers Acidic? A Carrier‐Mediated Diffusion Model for H + Transport in the Interstitial Fluid
Griffiths, J. R., McIntyre, D. J. O., Howe, F. A., & Stubbs, M. (2001) · Novartis Foundation symposium · doi:10.1002/0470868716.ch4 · Cited by 73
Hypoxia facilitates tumour cell detachment by reducing expression of surface adhesion molecules and adhesion to extracellular matrices without loss of cell viability
Hasan, N. M., Adams, G., Joiner, M. C., Marshall, J. F., & Hart, I. (1998) · British Journal of Cancer · doi:10.1038/bjc.1998.299 · Cited by 70
An examination of the effects of hypoxia, acidosis, and glucose starvation on the expression of metastasis-associated genes in murine tumor cells
Jang, A., & Hill, R. P. (1997) · Clinical & Experimental Metastasis · doi:10.1023/a:1018470709523 · Cited by 68
Tumor progression: Potential role of unstable genomic changes
Hill, R. P. (1990) · Cancer and Metastasis Reviews · doi:10.1007/bf00046340 · Cited by 65
Gene microarray analysis reveals a novel hypoxia signal transduction pathway in human hepatocellular carcinoma cells
Scandurro, A. B., Weldon, C. B., Figueroa, Y., Alam, J., & Beckman, B. S. (2001) · International Journal of Oncology · doi:10.3892/ijo.19.1.129 · Cited by 61
Effect of Hypoxia on Cellular Adhesion to Vitronectin and Fibronectin
Lash, G. E., Fitzpatrick, T. E., & Graham, C. H. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.5618 · Cited by 44
Plasminogen activator inhibitor type 1 in cytosolic tumor extracts predicts prognosis in low-risk breast cancer patients.
Grøndahl-Hansen, J., Christensen, I. J., Briand, P., Pappot, H., Mouridsen, H. T., Blichert-Toft, M., Danø, K., & Brünner, N. (1997) · PubMed · Cited by 42
Induction of basic helix-loop-helix protein DEC1 (BHLHB2)/Stra13/Sharp2 in response to the cyclic adenosine monophosphate pathway
Shen, M., Kawamoto, T., Teramoto, M., Makihira, S., Fujimoto, K., Yan, W., Noshiro, M., & Kato, Y. (2001) · European Journal of Cell Biology · doi:10.1078/0171-9335-00167 · Cited by 42
Both Increased Stability and Transcription Contribute to the Induction of the Urokinase Plasminogen Activator Receptor (uPAR) Message by Hypoxia
Maity, A. M., & Solomon, D. (2000) · Experimental Cell Research · doi:10.1006/excr.1999.4804 · Cited by 38
Mutagenicity and cytotoxicity of reactive oxygen and nitrogen species in the MN-11 murine tumor cell line
Sandhu, J. K., & Birnboim, H. C. (1997) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(97)00140-1 · Cited by 30
Quality assurance for 3D conformal radiation therapy.
Horsman, M. R., Nordsmark, M., & Overgaard, J. (1998) · PubMed · Cited by 28
Interstitial Fluid Pressure in Cervical Cancer
Milosevic, M., Fyles, A., & Hill, R. P. (2001) · American Journal of Clinical Oncology · doi:10.1097/00000421-200110000-00020 · Cited by 26
Expression of vascular endothelial growth factor by human renal cancer cells enhances angiogenesis of primary tumors and production of ascites but not metastasis to the lungs in nude mice
Kanayama, H.-O., Yano, S., Kim, S. J., Ozawa, S., Ellis, L. M., & Fidler, I. J. (1999) · Clinical & Experimental Metastasis · doi:10.1023/a:1006792007063 · Cited by 23
Comparison of autocrine mechanisms promoting motility in two metastatic cell lines: Human melanoma and ras‐transfected NIH3T3 cells
Seiki, M., Sato, H., Liotta, L. A., & Schiffmann, E. (1991) · International Journal of Cancer · doi:10.1002/ijc.2910490515 · Cited by 17
Expression of Autocrine Motility Factor/Phosphohexose Isomerase in Cos7 Cells
Lagana, A., Duchaîne, T. F., Raz, A., DesGroseillers, L., & Nabi, I. R. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.2904 · Cited by 16
A survey of in vivo growth characteristics and spontaneous metastasizing potentials of C3H mouse mammary tumors
Vaage, J. (1989) · International Journal of Cancer · doi:10.1002/ijc.2910430530 · Cited by 6

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Exploiting tumour hypoxia in cancer treatment
Brown, J. M., & Wilson, W. R. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1367 · Cited by 2,828
Defining normoxia, physoxia and hypoxia in tumours—implications for treatment response
McKeown, S. R. (2014) · The British Journal of Radiology · doi:10.1259/bjr.20130676 · Cited by 1,050
Tumor microenvironmental physiology and its implications for radiation oncology
Vaupel, P. W. (2004) · Seminars in Radiation Oncology · doi:10.1016/j.semradonc.2004.04.008 · Cited by 966
Chemical Design and Synthesis of Functionalized Probes for Imaging and Treating Tumor Hypoxia
Liu, J., Bu, W., & Shi, J. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.6b00525 · Cited by 842
A Microhomology-Mediated Break-Induced Replication Model for the Origin of Human Copy Number Variation
Hastings, P. J., Ira, G., & Lupski, J. R. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000327 · Cited by 818

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Authors: Subarsky, P., & Hill, R. P.
Affiliations: University of Toronto (CA)
Corresponding author: Hill, Richard P.
ORCID: Hill, Richard P.
Venue: Clinical & Experimental Metastasis
Publisher: Springer Science and Business Media LLC
Published: 2003-05
Volume: 20
Issue: 3
Pages: 237-250
ISSN: 0262-0898 (ISSN-L)
1573-7276
DOI: 10.1023/a:1022939318102
OpenAlex: W122518273
Cited by: 327
References: 132
Citations by year: 2026: 1 · 2024: 2 · 2023: 7 · 2022: 8 · 2021: 12 · 2020: 10 · 2019: 9 · 2018: 4 · 2017: 23 · 2016: 17 · 2015: 12 · 2014: 14 · 2013: 17 · 2012: 9
FWCI: 7.56
Type: journal article
Language: en
Open access: closed
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Clinical & Experimental Metastasis (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
Keywords: tumor hypoxia, tumor microenvironment, metastatic progression, genomic instability, genomic heterogeneity, epigenetic regulation, hypoxia-induced gene expression, anaerobic metabolism, angiogenesis, tissue remodeling, cell-cell contact, high-throughput screening, anti-metastatic agents
MeSH terms: Animals, Humans, Neoplasm Metastasis, Neoplasm Proteins, Neoplasms, Signal Transduction, Cell Hypoxia, Gene Expression Regulation, Neoplastic, Disease Progression

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The hypoxic tumour microenvironment and metastatic progression

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