Skip to main content
International Journal of Molecular Sciences logoLink to International Journal of Molecular Sciences
letter
. 2017 Mar 28;18(4):718. doi: 10.3390/ijms18040718

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

Daniela D’Arcangelo 1, Ezio M Nicodemi 1, Antonio Facchiano 1,*
Editors: Dario Marchetti1, Kurt Jellinger1
PMCID: PMC5412304  PMID: 28350319

To the Editor,

The review by Klumpp, L. et al. entitled Ion Channels in Brain Metastasis [1] discusses the role of ion channels in breast cancer, lung cancer and melanoma in metastatic tropism to the brain. The Authors debate the important role of ion channels in different steps of metastasis to the brain. Ion channels have shown aberrant expression in cancer cells and regulate tumor transformation as well as progression or resistance to therapy. Currently, there is a large growing interest toward such a field of investigation. In fact, since the date of publication of Klumpp, L. et al.’s manuscript (from September 2016 to date—beginning of March 2017) 37 additional manuscripts appeared in PubMed having “ion channel” and “cancer” in the “Title” or “Abstract” fields. In such studies, a few other channels have been shown to be involved in cancer set up and progression, although not only focused on brain metastases from breast, lung and melanoma cancers. 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.

Conflicts of Interest

The authors declare no conflict of interest.

References

  • 1.Klumpp L., Sezgin E.C., Eckert F., Huber S.M. Ion channels in brain metastasis. Int. J. Mol. Sci. 2016;17:1513. doi: 10.3390/ijms17091513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Biasiotta A., D’Arcangelo D., Passarelli F., Nicodemi E.M., Facchiano A. Ion channels expression and function are strongly modified in solid tumors and vascular malformations. J. Transl. Med. 2016;14:285. doi: 10.1186/s12967-016-1038-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Xu Y., Zhu J., Hu X., Wang C., Lu D., Gong C., Yang J., Zong L. CLIC1 inhibition attenuates vascular inflammation, oxidative stress, and endothelial injury. PLoS ONE. 2016;11:e0166790. doi: 10.1371/journal.pone.0166790. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Heo M.H., Kim J.Y., Hwang I., Ha E., Park K.U. Analgesic effect of quetiapine in a mouse model of cancer-induced bone pain. Korean J. Intern. Med. 2017:377. doi: 10.3904/kjim.2015.377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Ceylan G.G., Önalan E.E., Kuloğlu T., Aydoğ G., Keleş İ., Tonyali Ş., Ceylan C. Potential role of melastatin-related transient receptor potential cation channel subfamily M gene expression in the pathogenesis of urinary bladder cancer. Oncol. Lett. 2016;12:5235–5239. doi: 10.3892/ol.2016.5359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Mihara H., Suzuki N., Muhammad J.S., Nanjo S., Ando T., Fujinami H., Kajiura S., Hosokawa A., Sugiyama T. Transient receptor potential vanilloid 4 (TRPV4) silencing in Helicobacter pylori-infected human gastric epithelium. Helicobacter. 2016;22:e12361. doi: 10.1111/hel.12361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Derouiche S., Mariot P., Warnier M., Vancauwenberghe E., Bidaux G., Gosset P., Mauroy B., Bonnal J.-L., Slomianny C., Delcourt P., et al. Activation of TRPA1 channel by antibacterial agent triclosan induces VEGF secretion in human prostate cancer stromal cells. Cancer Prev. Res. 2017;10:177–187. doi: 10.1158/1940-6207.CAPR-16-0257. [DOI] [PubMed] [Google Scholar]
  • 8.Chen Z., Tang C., Zhu Y., Xie M., He D., Pan Q., Zhang P., Hua D., Wang T., Jin L., et al. TrpC5 regulates differentiation through the Ca2+/Wnt5a signalling pathway in colorectal cancer. Clin. Sci. 2017;131:227–237. doi: 10.1042/CS20160759. [DOI] [PubMed] [Google Scholar]
  • 9.Pei J.V., Kourghi M., de Ieso M.L., Campbell E.M., Dorward H.S., Hardingham J.E., Yool A.J. Differential inhibition of water and ion channel activities of mammalian aquaporin-1 by two structurally related bacopaside compounds derived from the medicinal plant bacopa monnieri. Mol. Pharmacol. 2016;90:496–507. doi: 10.1124/mol.116.105882. [DOI] [PubMed] [Google Scholar]

Articles from International Journal of Molecular Sciences are provided here courtesy of Multidisciplinary Digital Publishing Institute (MDPI)

RESOURCES