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In vivo imaging and characterization of hypoxia-induced neovascularization and tumor invasion

Lungu, Gina F. and Li, Meng-Lin and Xie, Xueyi and Wang, Lihong V. and Stoica, George (2007) In vivo imaging and characterization of hypoxia-induced neovascularization and tumor invasion. International Journal of Oncology, 30 (1). pp. 45-54. ISSN 1019-6439. doi:10.3892/ijo.30.1.45.

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Hypoxia is a critical event in tumor progression and angiogenesis. Hypoxia can be detected noninvasively by a novel spectroscopic photoacoustic tomography technology (SPAT) and this finding is supported by our molecular biology investigation aimed to elucidate the etiopathogenesis of SPAT detected hypoxia and angiogenesis. The present study provides an integrated approach to define oxygen status (hypoxia) of intracranial tumor xenografts using spectroscopic photoacoustic tomography. Brain tumors can be identified based on their distorted vascular architecture and oxygen saturation (SO2) images. Noninvasive in vivo tumor oxygenation imaging using SPAT is based on the spectroscopic absorption differences between oxyhemoglobin (O2Hb) and deoxyhemoblobin (HHb). Sprague-Dawley rats inoculated intracranially with ENU1564, a carcinogen-induced rat mammary adenocarcinoma cell line, were imaged with SPAT three weeks post inoculation. Proteins important for tumor angiogenesis and invasion were detected in hypoxic brain foci identified by SPAT and were elevated compared with control brain. Immunohistochemistry, Western blotting, and semi-quantitative RT-PCR showed that HIF-1 α, VEGF-A, and VEGFR2 (Flk-1) protein and mRNA expression levels were significantly higher (P<0.05) in brain tumor tissues compared to normal brain. Gelatin zymography and RT-PCR demonstrated the upregulation of MMP-9 in tumor foci compared with brain control. Together these results suggest the critical role of hypoxia in driving tumor angiogenesis and invasion through upregulation of target genes important for these functions. Moreover this report validates our hypothesis that a novel noninvasive technology (SPAT) developed in our laboratory is suitable for detection of tumors, hypoxia, and angiogenesis.

Item Type:Article
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Wang, Lihong V.0000-0001-9783-4383
Stoica, George0000-0001-8071-4828
Additional Information:© 2007 Spandidos Publications. Received June 6, 2006; Accepted July 12, 2006; Published online on: Monday, January 1, 2007. We are grateful to Dr G. Bratton for critical reading of the manuscript. This work was supported by a National Institute of Health grant (no. R01-N5046214-01).
Funding AgencyGrant Number
Subject Keywords:HIF-1α, hypoxia, MMP-9, spectroscopic photoacoustic tomography, VEGF, VEGFR2
Issue or Number:1
Record Number:CaltechAUTHORS:20161005-083813036
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Official Citation:Lungu, G. F., Li, M., Xie, X., Wang, L. V., Stoica, G."In vivo imaging and characterization of hypoxia-induced neovascularization and tumor invasion". International Journal of Oncology 30.1 (2007): 45-54
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:70858
Deposited By: Tony Diaz
Deposited On:05 Oct 2016 16:21
Last Modified:11 Nov 2021 04:36

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