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Imatinib increases ...
Imatinib increases oxygen delivery in extracellular matrix-rich but not in matrix-poor experimental carcinoma
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- Burmakin, Mikhail (author)
- Uppsala University,Karolinska Institutet,Uppsala universitet,Ludwiginstitutet för cancerforskning,Science for Life Laboratory, SciLifeLab,Karolinska Inst, Div Vasc Biol, Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden.
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- van Wieringen, Tijs, 1979- (author)
- Uppsala University,Uppsala universitet,Ludwiginstitutet för cancerforskning,Science for Life Laboratory, SciLifeLab,Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England.,University of Birmingham
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- Olsson, Olof (author)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine
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- Stuhr, Linda (author)
- Univ Bergen, Dept Biomed, Bergen, Norway.,University of Bergen
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- Åhgren, Aive (author)
- Uppsala University,Uppsala universitet,Ludwiginstitutet för cancerforskning,Science for Life Laboratory, SciLifeLab
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- Heldin, Carl-Henrik, 1952- (author)
- Uppsala University,Uppsala universitet,Ludwiginstitutet för cancerforskning,Science for Life Laboratory, SciLifeLab
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- Reed, Rolf K. (author)
- Univ Bergen, Dept Biomed, Bergen, Norway.;Univ Bergen, Ctr Canc Biomarkers CCBIO, Bergen, Norway.,University of Bergen
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- Rubin, Kristofer (author)
- Lund University,Lunds universitet,Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Lund Univ, Dept Lab Med, S-22363 Lund, Sweden.;Lund Univ, Dept Expt Med Sci, BMC D10, S-22381 Lund, Sweden.,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine
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- Hellberg, Carina (author)
- Uppsala University,Uppsala universitet,Ludwiginstitutet för cancerforskning,Science for Life Laboratory, SciLifeLab,Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England.,University of Birmingham
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(creator_code:org_t)
- 2017-02-23
- 2017
- English.
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In: Journal of Translational Medicine. - : BioMed Central. - 1479-5876. ; 15
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Abstract
Subject headings
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- Background: Imatinib causes increased turnover of stromal collagen, reduces collagen fibril diameter, enhances extracellular fluid turnover and lowers interstitial fluid pressure (IFP) in the human colonic carcinoma KAT-4/HT-29 (KAT-4) xenograft model. Methods: We compared the effects of imatinib on oxygen levels, vascular morphology and IFP in three experimental tumor models differing in their content of a collagenous extracellular matrix. Results: Neither the KAT4 and CT-26 colonic carcinoma models, nor B16BB melanoma expressed PDGF beta-receptors in the malignant cells. KAT-4 tumors exhibited a well-developed ECM in contrast to the other two model systems. The collagen content was substantially higher in KAT-4 than in CT-26, while collagen was not detectable in B16BB tumors. The pO(2) was on average 5.4, 13.9 and 19.3 mmHg in KAT-4, CT-26 and B16BB tumors, respectively. Treatment with imatinib resulted in similar pO(2)-levels in all three tumor models but only in KAT-4 tumors did the increase reach statistical significance. It is likely that after imatinib treatment the increase in pO(2) in KAT-4 tumors is caused by increased blood flow due to reduced vascular resistance. This notion is supported by the significant reduction observed in IFP in KAT-4 tumors after imatinib treatment. Vessel area varied between 4.5 and 7% in the three tumor models and was not affected by imatinib treatment. Imatinib had no effect on the fraction of proliferating cells, whereas the fraction of apoptotic cells increased to a similar degree in all three tumor models. Conclusion: Our data suggest that the effects of imatinib on pO(2)-levels depend on a well-developed ECM and provide further support to the suggestion that imatinib acts by causing interstitial stroma cells to produce a less dense ECM, which would in turn allow for an increased blood flow. The potential of imatinib treatment to render solid tumors more accessible to conventional treatments would therefore depend on the degree of tumor desmoplasia.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Hypoxia
- Interstitial fluid pressure
- Receptor tyrosine kinase
- Tumor stroma
- Hypoxia
- Interstitial fluid pressure
- Receptor tyrosine kinase
- Tumor stroma
Publication and Content Type
- ref (subject category)
- art (subject category)
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