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Molecular imaging of aquaglycero-aquaporins: its potential for cancer characterization
Yuriko Saito1, Takako Furukawa, Takayuki Obata
1Molecular Imaging Center, National Institute of Radiological Sciences, 4–9–1 Anagawa, Inage-ku, Chiba 263–8555, Japan.
Abstract:
Aquaglycero-aquaporins (agAQPs) are one of the water channel proteins located in the cell membrane that transport not only water but also some small solutes such as glycerol. Since agAQPs are involved in cancer proliferation and malignancy, it might be possible to utilize them as new targets for cancer molecular imaging. In this study, we investigated whether agAQPs can be specifically targeted by using [(14)C]-labeled glycerol ([(14)C]glycerol), which passes through agAQPs. In the in vitro experiments, comparing the cancer cell lines with different expression levels of AQP3 and AQP9, major agAQPs known to be expressed in cancers, and examining the effect of their inhibitors on these cells, the expression of AQP3 and AQP9 in cell lines was shown to be closely related to [(14)C]glycerol uptake. When [(14)C]glycerol was injected into tumor-bearing mice, Spearman's rank coefficient analysis revealed that radioactivity levels in tumor and in plasma were mutually correlated only in tumors expressing agAQPs at a high level. These results indicate the possibility of using agAQPs as new targets to characterize cancer using radiolabeled glycerol as a molecular probe.
Insights
Radiolabeled glycerol uptake by cancer cells correlates with aquaglyceroporin (agAQP) expression. This suggests agAQPs can be targeted for cancer molecular imaging using radiolabeled glycerol as a probe.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Aquaglyceroporins (agAQPs) are cell membrane proteins facilitating water and glycerol transport.
- agAQPs are implicated in cancer proliferation and malignancy, suggesting their potential as molecular imaging targets.
Purpose of the Study:
- To investigate the potential of targeting agAQPs for cancer molecular imaging.
- To evaluate the use of [(14)C]-labeled glycerol as a molecular probe for agAQP-targeted imaging.
Main Methods:
- In vitro experiments using cancer cell lines with varying AQP3 and AQP9 expression levels.
- In vivo studies involving [(14)C]glycerol injection into tumor-bearing mice.
- Analysis of radioactivity correlation between tumors and plasma using Spearman's rank coefficient.
Main Results:
- [(14)C]glycerol uptake in cancer cells directly correlated with AQP3 and AQP9 expression.
- Radioactivity levels in tumors and plasma showed a significant correlation only in tumors with high agAQP expression.
- Inhibitor studies confirmed the role of agAQPs in glycerol transport.
Conclusions:
- agAQPs are viable targets for cancer molecular imaging.
- [(14)C]glycerol serves as a potential molecular probe for characterizing cancers expressing high levels of agAQPs.
- This approach may enable novel strategies for cancer diagnosis and monitoring.
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