Visualization of hypoxia in microscopic tumors by immunofluorescent microscopy Journal Article


Authors: Li, X. F. ; Carlin, S.; Urano, M.; Russell, J.; Ling, C. C.; O'Donoghue, J. A.
Article Title: Visualization of hypoxia in microscopic tumors by immunofluorescent microscopy
Abstract: Tumor hypoxia is commonly observed in primary solid malignancies but the hypoxic status of subclinical micrometastatic disease is largely unknown. The distribution of hypoxia in microscopic tumors was studied in animal models of disseminated peritoneal disease and intradermal (i.d.) growing tumors. Tumors derived from human colorectal adenocarcinoma cell lines HT29 and HCT-8 ranged in size from a few hundred microns to several millimeters in diameter. Hypoxia was detected by immunofluorescent visualization of pimonidazole and the hypoxia-regulated protein carbonic anhydrase 9. Tumor blood perfusion, cellular proliferation, and vascularity were visualized using Hoechst 33342, bromodeoxyuridine, and CD31 staining, respectively. In general, tumors of <1 mm diameter were intensely hypoxic, poorly perfused, and possessed little to no vasculature. Larger tumors (∼1-4 mm diameter) were well perfused with widespread vasculature and were not significantly hypoxic. Patterns of hypoxia in disseminated peritoneal tumors and i.d. tumors were similar. Levels of hypoxia in microscopic peritoneal tumors were reduced by carbogen breathing. Peritoneal and i.d. tumor models are suitable for studying hypoxia in microscopic tumors. If the patterns of tumor hypoxia in human patients are similar to those observed in these animal experiments, then the efficacy of systemic treatments of micrometastatic disease may be compromised by hypoxic resistance. ©2007 American Association for Cancer Research.
Keywords: controlled study; ascites; nonhuman; adenocarcinoma; cell proliferation; mouse; animals; mice; peritoneal neoplasms; tumor volume; oxygen; animal experiment; animal model; colonic neoplasms; cell line, tumor; vascularization; carbonate dehydratase ix; mice, nude; transplantation, heterologous; microscopy, fluorescence; hoe 33342; pimonidazole; cell hypoxia; neoplasm transplantation; ascites tumor; ht29 cells; peritoneum tumor; immunofluorescence microscopy; cd31 antigen; broxuridine; carbogen; carbon dioxide; tumor blood flow; colorectal adenocarcinoma
Journal Title: Cancer Research
Volume: 67
Issue: 16
ISSN: 0008-5472
Publisher: American Association for Cancer Research  
Date Published: 2007-08-15
Start Page: 7646
End Page: 7653
Language: English
DOI: 10.1158/0008-5472.can-06-4353
PUBMED: 17699769
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 23" - "Export Date: 17 November 2011" - "CODEN: CNREA" - "Source: Scopus"
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MSK Authors
  1. Xiao-Feng Li
    11 Li
  2. James Russell
    41 Russell
  3. Sean Denis Carlin
    83 Carlin
  4. C Clifton Ling
    331 Ling
  5. Moneyasu Urano
    23 Urano