Potential role of melastatin-related transient receptor potential cation channel subfamily M gene expression in the pathogenesis of urinary bladder cancer

Abstract

Abstract. Urinary bladder cancer is one of the most common malignancies of the urinary tract. Ion channels and calcium homeostasis are involved in almost all basic cellular mechanisms. The transient receptor potential cation channel subfamily M (TRPM) takes its name from the melastatin protein, which is classified as potential tumor suppressor. To the best of our knowledge, there have been no previous studies in the literature investigating the role of these ion channels in bladder cancer. The present study aimed to determine whether bladder cancer is associated with mRNA expression levels of TRPM ion channel genes, and whether there is the potential to conduct further studies to establish novel treatment modalities. The present study included a total of 47 subjects, of whom 40 were bladder cancer patients and 7 were controls. Following the histopathological evaluation for bladder carcinoma, the mRNA and protein expression of TRPM were examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry in tumor and normal tissues, in order to determine whether there is a difference in the expression of these channels in tumor and normal tissues. Immunoreactivity for TRPM2, TRPM4, TRPM7 and TRPM8 was observed in epithelial bladder cells in the two groups. RT-qPCR revealed a significant increase in TRPM7 expression in bladder cancer tissue compared to the controls (healthy bladder tissue), whereas no differences in TRPM2 or TRPM4 expression levels were observed. There were significant reductions in the expression levels of TRPM5 and TRPM8 in bladder cancer tissues. In the present study, the effects of TRP ion channels on the formation of bladder cancer was investigated. This study is instructive for TRPM2, TRPM4, TRPM5, TRPM7 and TRPM8 and their therapeutic role in bladder cancer. The results support the fact that these gens can be novel targets and can also be tested for during the treatment of bladder cancer.

TRPM4 in Cancer—A New Potential Drug Target

“…TRPM4 expression levels have been investigated in a number of different cancers ( Figure 2 ) [ 32 , 33 , 34 , 38 , 39 , 40 , 41 , 101 , 102 , 103 , 104 , 105 , 106 ]. In most studies, TRPM4 protein expression levels were reported to be increased in tumor samples compared to healthy tissue.…”

<p>TRPM8 Inhibition Regulates the Proliferation, Migration and ROS Metabolism of Bladder Cancer Cells</p>

“… 15 – 17 Ceylan et al observed a significant decrease in the expression of TRPM8 in bladder cancer tissues using qRT-PCR and immunohistochemistry analysis. 18 In contrast, Xiao et al reported a significant upregulation of TRPM8 in BCa tissues compared with matched noncancerous tissues, and its expression was associated with the histological grade and tumor stage. 19 Based on these controversial results, the association between the expression of TRPM8 and the development of BCa must be clarified.…”

Letter to the Editor: “Ion Channels in Brain Metastasis”—Ion Channels in Cancer Set up and Metastatic Progression

“…For instance, we [ 2 ] evaluated the expression of ninety ion-channel genes in 3673 human biopsies, in five different solid tumors (bladder cancer, breast cancer, glioblastoma, lung cancer and melanoma). We [ 2 ] and others [ 3 , 4 , 5 , 6 , 7 , 8 , 9 ] have shown a key role of ion channels in tumors common to Klumpp, L. et al, namely lung cancer, breast cancer and melanoma, as well as in other cancers such as glioblastoma, bladder cancer and colorectal cancer. These channels are calcium channel voltage-dependent (CACNA1D); FXYD domain-containing ion transport regulators (FXYD3, FXYD5); chloride intracellular channels (CLIC1); glutamate receptors (HTR3A); potassium channel voltage-gated channels (KCNE3, KCNE4, KCNN4); transient receptor potential cation channels (TRPA1, TRPC5, TRPM3, TRPV4) and Aquaporins (AQPs).…”

“…Such a list may somehow integrate the scenario depicted by Klumpp, L. et al As we underlined in our study, all such cancers have different histological origin but they have endothelial and vascular alterations in common. The role of ion channels in vascular alteration occurring in the metastatic process is clearly recognized but still not completely elucidated, as discussed by Klumpp, L. et al Therefore, we believe that all these ion channels reported by Klumpp, L. et al [ 1 ]., us [ 2 ] and others [ 3 , 4 , 5 , 6 , 7 , 8 , 9 ] may have a mechanistic role in the primary tumor set up as well as in the metastatic progression toward the brain and other organs.…”