Molecular Imaging of Aquaglycero-Aquaporins: Its Potential for Cancer Characterization

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.

Metabolism, toxicity and anticancer activities of arsenic compounds

“…For example, the chronic myeloid leukemia cell line (K562) is recognized less sensitive towards iAs III treatment because of lacking adequate expression of AQP9 [69]. Moreover, when AQP3 gene was knocked down in human lung adenocarcinoma cell line (CL3), it was found that the CL3 cells became more resistant to iAs III [70], indicating the AQPs are at least involved in cellular susceptibility towards iAs III .…”

Clinical value and molecular mechanism of AQGPs in different tumors

“…The involvement of AQP9 in glycerol transportation continues to draw attention from researchers, and now it has been extended to cancer research. In several cancer cell lines, the expression of AQP9 was related to the uptake of [14C]-labeled glycerol [ 138 ]. Another experiment in a rat hepatocellular carcinoma model found that the expression of AQP9 was present at a low level before tumorigenesis, while it was significantly increased in the early stage of hepatocellular carcinoma.…”

Aquaglyceroporins: Drug Targets for Metabolic Diseases?

“…The potential beneficial use of AQP3 inhibitors or modulators (decreasing AQP3 expression) remains to be evaluated for cancer treatment. In addition, radiolabeled glycerol could be used as a molecular probe targeting aquaglyceroporins to estimate their expression in different tissues in vivo , including tumors ( Saito et al, 2013 ).…”