Valerio FarfarielloNatalia PrevarskayaDimitra GkikaChapter

First Online: 01 August 2020

Part of the Reviews of Physiology, Biochemistry and Pharmacology book series (REVIEWS, volume 181)Abstract

In the last three decades, a growing number of studies have implicated ion channels in all essential processes of prostate carcinogenesis, including cell proliferation, apoptosis, migration, and angiogenesis. The changes in the expression of individual ion channels show a specific profile, making these proteins promising clinical biomarkers that may enable better molecular subtyping of the disease and lead to more rapid and accurate clinical decision-making. Expression profiles and channel function are mainly based on the tumoral tissue itself, in this case, the epithelial cancer cell population. To date, little data on the ion channel profile of the cancerous prostate stroma are available, even though tumor interactions with the microenvironment are crucial in carcinogenesis and each distinct population plays a specific role in tumor progression. In this review, we describe ion channel expression profiles specific for the distinct cell population of the tumor microenvironment (stromal, endothelial, neuronal, and neuroendocrine cell populations) and the technical approaches used for efficient separation and screening of these cell populations.

KeywordsCalcium Cancer biomarkers Chloride Ion channels Neuroendocrine cells Potassium Stroma cells Transient receptor potential Tumor-derived endothelial cells 

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NotesAcknowledgments

English language, grammar, punctuation, spelling, and overall style by the highly qualified native English-speaking editors at American Journal Experts (certificate number EDCC-3B24-C703-F3F2-FDE9).

Conflict of Interest

The authors declare no conflict of interest in the manuscript.

Funding

All authors were supported by grants from the Ministère de l’Education Nationale, the Institut National de la Santé et de la Recherche Medicale (INSERM), and La Ligue contre le cancer. DG was supported by the Institut Universitaire de France (IUF). VF was supported by Institut National du Cancer (INCA).

References

Alphonso A, Alahari SK (2009) Stromal cells and integrins: conforming to the needs of the tumor microenvironment. Neoplasia 11(12):1264–1271

PubMedPubMedCentralGoogle Scholar

Aragon-Ching JB, Madan RA, Dahut WL (2010) Angiogenesis inhibition in prostate cancer: current uses and future promises. J Oncol 2010:361836

PubMedPubMedCentralGoogle Scholar

Bai VU, Murthy S, Chinnakannu K, Muhletaler F, Tejwani S, Barrack ER et al (2010) Androgen regulated TRPM8 expression: a potential mRNA marker for metastatic prostate cancer detection in body fluids. Int J Oncol 36(2):443–450

PubMedGoogle Scholar

Bernardini M, Brossa A, Chinigo G, Grolez GP, Trimaglio G, Allart L et al (2019) Transient receptor potential channel expression signatures in tumor-derived endothelial cells: functional roles in prostate cancer angiogenesis. Cancers 11(7):E956

PubMedGoogle Scholar

Berry PA, Birnie R, Droop AP, Maitland NJ, Collins AT (2011) The calcium sensor STIM1 is regulated by androgens in prostate stromal cells. Prostate 71(15):1646–1655

PubMedGoogle Scholar

Bidaux G, Flourakis M, Thebault S, Zholos A, Beck B, Gkika D et al (2007) Prostate cell differentiation status determines transient receptor potential melastatin member 8 channel subcellular localization and function. J Clin Invest 117(6):1647–1657

PubMedPubMedCentralGoogle Scholar

Bloch M, Ousingsawat J, Simon R, Schraml P, Gasser TC, Mihatsch MJ et al (2007) KCNMA1 gene amplification promotes tumor cell proliferation in human prostate cancer. Oncogene 26(17):2525–2534

PubMedGoogle Scholar

Bray M-A, Singh S, Han H, Davis CT, Borgeson B, Hartland C et al (2016) Cell painting, a high-content image-based assay for morphological profiling using multiplexed fluorescent dyes. Nat Protoc 11(9):1757–1774

PubMedPubMedCentralGoogle Scholar

Brizzi MF, Tarone G, Defilippi P (2012) Extracellular matrix, integrins, and growth factors as tailors of the stem cell niche. Curr Opin Cell Biol 24(5):645–651

PubMedGoogle Scholar

Bussolati B, Grange C, Camussi G (2011) Tumor exploits alternative strategies to achieve vascularization. FASEB J 25(9):2874–2882

PubMedGoogle Scholar

Caprodossi S, Lucciarini R, Amantini C, Nabissi M, Canesin G, Ballarini P et al (2007) Transient receptor potential vanilloid type 2 (TRPV2) expression in normal urothelium and in urothelial carcinoma of human bladder: correlation with the pathologic stage. Eur Urol 54(3):612–620

PubMedGoogle Scholar

Carmeliet P, Jain RK (2011) Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases. Nat Rev Drug Discov 10(6):417–427

PubMedGoogle Scholar

Cunha GR, Hayward SW, Wang YZ (2002) Role of stroma in carcinogenesis of the prostate. Differentiation 70(9):473–485

PubMedGoogle Scholar

Cunha GR, Hayward SW, Wang YZ, Ricke WA (2003) Role of the stromal microenvironment in carcinogenesis of the prostate. Int J Cancer 107(1):1–10

PubMedGoogle Scholar

Dakhova O, Ozen M, Creighton CJ, Li R, Ayala G, Rowley D et al (2009) Global gene expression analysis of reactive stroma in prostate cancer. Clin Cancer Res 15(12):3979–3989

PubMedPubMedCentralGoogle Scholar

De Bock K, Cauwenberghs S, Carmeliet P (2011) Vessel abnormalization: another hallmark of cancer? Molecular mechanisms and therapeutic implications. Curr Opin Genet Dev 21(1):73–79

PubMedGoogle Scholar

Derouiche S, Mariot P, Warnier M, Vancauwenberghe E, Bidaux G, Gosset P et al (2017) Activation of TRPA1 channel by antibacterial agent triclosan induces VEGF secretion in human prostate cancer stromal cells. Cancer Prev Res 10(3):177–187

Google Scholar

Domazet B, Maclennan GT, Lopez-Beltran A, Montironi R, Cheng L (2008) Laser capture microdissection in the genomic and proteomic era: targeting the genetic basis of cancer. Int J Clin Exp Pathol 1(6):475–488

PubMedPubMedCentralGoogle Scholar

Du C, Zheng Z, Li D, Chen L, Li N, Yi X et al (2016) BKCa promotes growth and metastasis of prostate cancer through facilitating the coupling between αvβ3 integrin and FAK. Oncotarget 7(26):40174–40188

PubMedPubMedCentralGoogle Scholar

Dubois C, Vanden Abeele F, Lehen’kyi V, Gkika D, Guarmit B, Lepage G et al (2014) Remodeling of channel-forming ORAI proteins determines an oncogenic switch in prostate cancer. Cancer Cell 26(1):19–32

PubMedGoogle Scholar

Duranti C, Arcangeli A (2019) Ion channel targeting with antibodies and antibody fragments for cancer diagnosis. Antibodies 8(2):33

PubMedCentralGoogle Scholar

Emmert-Buck MR, Bonner RF, Smith PD, Chuaqui RF, Zhuang Z, Goldstein SR et al (1996) Laser capture microdissection. Science 274(5289):998–1001

PubMedGoogle Scholar

Faulkner S, Jobling P, March B, Jiang CC, Hondermarck H (2019) Tumor neurobiology and the war of nerves in cancer. Cancer Discov 9(6):702–710

PubMedGoogle Scholar

Ferlay J, Colombet M, Soerjomataram I, Dyba T, Randi G, Bettio M et al (2018) Cancer incidence and mortality patterns in Europe: estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer 103:356–387

Google Scholar

Fiorio Pla A, Grange C, Antoniotti S, Tomatis C, Merlino A, Bussolati B et al (2008) Arachidonic acid-induced Ca2+ entry is involved in early steps of tumor angiogenesis. Mol Cancer Res 6(4):535–545

PubMedGoogle Scholar

Fiorio Pla A, Genova T, Pupo E, Tomatis C, Genazzani A, Zaninetti R et al (2010) Multiple roles of protein kinase a in arachidonic acid-mediated Ca2+ entry and tumor-derived human endothelial cell migration. Mol Cancer Res 8(11):1466–1476

PubMedGoogle Scholar

Fiorio Pla A, Brossa A, Bernardini M, Genova T, Grolez G, Villers A et al (2014) Differential sensitivity of prostate tumor derived endothelial cells to sorafenib and sunitinib. BMC Cancer 14(1):939

PubMedPubMedCentralGoogle Scholar

Fraser SP, Grimes JA, Diss JKJ, Stewart D, Dolly JO, Djamgoz MBA (2003) Predominant expression of Kv1.3 voltage-gated K+ channel subunit in rat prostate cancer cell lines: electrophysiological, pharmacological and molecular characterisation. Pflugers Arch 446(5):559–571

PubMedGoogle Scholar

Fukami K, Sekiguchi F, Yasukawa M, Asano E, Kasamatsu R, Ueda M et al (2015) Functional upregulation of the H2S/Cav3.2 channel pathway accelerates secretory function in neuroendocrine-differentiated human prostate cancer cells. Biochem Pharmacol 97(3):300–309

PubMedGoogle Scholar

Gackière F, Bidaux G, Delcourt P, Van Coppenolle F, Katsogiannou M, Dewailly E et al (2008) CaV3.2 T-type calcium channels are involved in calcium-dependent secretion of neuroendocrine prostate cancer cells. J Biol Chem 283(15):10162–10173

PubMedGoogle Scholar

Gackière F, Warnier M, Katsogiannou M, Derouiche S, Delcourt P, Dewailly E et al (2013) Functional coupling between large-conductance potassium channels and Cav3.2 voltage-dependent calcium channels participates in prostate cancer cell growth. Biol Open 2(9):941–951

PubMedPubMedCentralGoogle Scholar

Gkika D, Prevarskaya N (2011) TRP channels in prostate cancer: the good, the bad and the ugly? Asian J Androl 13(May):673–676

PubMedPubMedCentralGoogle Scholar

Gkika D, Flourakis M, Lemonnier L, Prevarskaya N (2010) PSA reduces prostate cancer cell motility by stimulating TRPM8 activity and plasma membrane expression. Oncogene 29(32):4611–4616

PubMedGoogle Scholar

Gkika D, Lemonnier L, Shapovalov G, Gordienko D, Poux C, Bernardini M et al (2015) TRP channel-associated factors are a novel protein family that regulates TRPM8 trafficking and activity. J Cell Biol 208(1):89–107

PubMedPubMedCentralGoogle Scholar

Grobholz R, Griebe M, Sauer CG, Michel MS, Trojan L, Bleyl U (2005) Influence of neuroendocrine tumor cells on proliferation in prostatic carcinoma. Hum Pathol 36(5):562–570

PubMedGoogle Scholar

Gustafsdottir SM, Ljosa V, Sokolnicki KL, Anthony Wilson J, Walpita D, Kemp MM et al (2013) Multiplex cytological profiling assay to measure diverse cellular states. PLoS One 8(12):e80999.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847047/PubMedPubMedCentralGoogle Scholar

Hägglöf C, Bergh A (2012) The stroma-a key regulator in prostate function and malignancy. Cancers 4(2):531–548

PubMedPubMedCentralGoogle Scholar

Hall M, Todd B, Allen ED, Nguyen N, Kwon Y-J, Nguyen V et al (2018) Androgen receptor signaling regulates T-type Ca2+ channel expression and neuroendocrine differentiation in prostate cancer cells. Am J Cancer Res 8(4):732–747

PubMedPubMedCentralGoogle Scholar

Han Y, Liu C, Zhang D, Men H, Huo L, Geng Q et al (2019) Mechanosensitive ion channel Piezo1 promotes prostate cancer development through the activation of the Akt/mTOR pathway and acceleration of cell cycle. Int J Oncol 55(3):629–644

PubMedPubMedCentralGoogle Scholar

Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674

Google Scholar

Hendijani F (2017) Explant culture: an advantageous method for isolation of mesenchymal stem cells from human tissues. Cell Prolif 50(2):e12334

PubMedCentralGoogle Scholar

Holzmann C, Kappel S, Kilch T, Jochum MM, Urban SK, Jung V et al (2015) Transient receptor potential melastatin 4 channel contributes to migration of androgen-insensitive prostate cancer cells. Oncotarget 6(39):41783–41793

PubMedPubMedCentralGoogle Scholar

Hwang C, Heath EI (2010) Angiogenesis inhibitors in the treatment of prostate cancer. J Hematol Oncol 3:26

PubMedPubMedCentralGoogle Scholar

Hwang B, Lee JH, Bang D (2018) Single-cell RNA sequencing technologies and bioinformatics pipelines. Exp Mol Med 50(8):96

PubMedCentralGoogle Scholar

Islam S, Kjällquist U, Moliner A, Zajac P, Fan J-B, Lönnerberg P et al (2011) Characterization of the single-cell transcriptional landscape by highly multiplex RNA-seq. Genome Res 21(7):1160–1167

PubMedPubMedCentral