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Transcriptomic data analysis of melanocytes and melanoma cell lines of LAT transporter genes for precise medicine

Identyfikatory
Warianty tytułu
Konferencja
4th Jagiellonian Symposium on Advances in Particle Physics and Medicine, Krakow, 10-15 July 2022
Języki publikacji
EN
Abstrakty
EN
Background: Boron Neutron Capture Therapy (BNCT) is a two-step treatment that can be used in some types of cancers. It involves administering a compound containing boron atoms to the patient and irradiating the affected area of the body with a neutron beam. The success of the therapy depends mainly on the delivery of the boron isotope (10B) to the tumor using an appropriate boron carrier. One of the boron carriers used is boronophenylalanine (BPA). Therefore, in research on the use of boron carriers, it is also important to know the mechanisms of its uptake by cells. Aim: To study the expression of LAT family genes in two melanoma (high melanotic WM115 and low melanotic WM266-4) cell lines and melanocytes (HEMa-Lp) which are responsible for the transport the BPA into cells. Methods: To normalize data from the transcriptomic analysis, the ratio of the median method was used. This allowed the samples to be compared with each other. Comparison metrics included log-fold change (LFC) values. The heatmap of LFC values and the cluster map were created. These graphs show the similarities and differences between the samples. Results: Transcriptomic data show that in melanocytes, LFC for SLC7A5 (LAT1) and SLC3A2 (4Fhc) was higher than in melanoma cell lines, which corresponded with their melanin content. Conclusion: Our results indicate overexpression of BPA transporter genes in normal cells (melanocytes), which may suggest the highest level of these proteins in melanocytes compared to less melanotic melanoma. Therefore, for BNCT, the use of BPA as the 10B carrier will require additional qualifying tests of amino acid transporter expression for patients and specific tumors to develop a personalized BNCT.
Rocznik
Strony
144--150
Opis fizyczny
Bibliogr. 29 poz., rys.
Twórcy
  • Center for Theranostics, JagiellonianUniversity, Kopernika 40 St., 31-034 Krakw, Poland
  • Department of Medical Physics, M. Smoluchowski Institute of Physics, Jagiellonian University, Łojasiewicza 11 St., 30-348 Kraków, Poland Center for Theranostics, Jagiellonian University, Kopernika 40 St., 31-034 Kraków, Poland
  • Total-Body Jagiellonian-PET Laboratory, Jagiellonian University, Kraków, Poland
autor
  • Department of Glycoconjugate Biochemistry, Institute of Zoology and Biomedical Research, Jagiellonian University, Gronostajowa 9 St., 30-387 Kraków, Poland
  • Center for Theranostics, Jagiellonian University, Kopernika 40 St., 31-034 Kraków, Poland
  • Total-Body Jagiellonian-PET Laboratory, Jagiellonian University, Kraków, Poland
  • Department of Experimental Particle Physics and Applications, M. Smoluchowski Institute of Physics, Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University, Łojasiewicza 11 St., 30-348 Krakow, Poland
  • Center for Theranostics, Jagiellonian University,Kopernika 40 St., 31-034 Krakw, Poland; Total-Body Jagiellonian-PET Laboratory, Jagiellonian University, Krakw, Poland
  • Department of Medical Physics, M. Smoluchowski Institute of Physics, Jagiellonian University, Łojasiewicza 11 St., 30-348 Kraków, Poland
Bibliografia
  • [1] Kanai Y. Amino acid transporter LAT1 (SLC7A5) as a molecular target for cancer diagnosis and therapeutics. Pharmacol Ther. 2022;230:107964.
  • [2] Alles SRA, Gomez K, Moutal A, Khanna R. Putative roles of SLC7A5 (LAT1) transporter in pain. Neurobiology of Pain. 2020;8:100050.
  • [3] Achmad A, Lestari S, Holik HA, Rahayu D, Bashari MH, Faried A, et al. Highly specific l-type amino acid transporter 1 inhibition by JPH203 as a potential pancancer treatment. Processes. 2021;9:1-15.
  • [4] Wang Q, Holst J. L-type amino acid transport and cancer: Targeting the mTORC1 pathway to inhibit neoplasia. Am J Cancer Res. 2015;5:1281-94.
  • [5] Scalise M, Galluccio M, Console L, Pochini L, Indiveri C. The human SLC7A5 (LAT1): The intriguing histidine/large neutral amino acid transporter and its relevance to human health. Front Chem. 2018;6:1-12.
  • [6] Higuchi K, Sakamoto S, Ando K, Maimaiti M, Takeshita N, Okunushi K, et al. Characterization of the expression of LAT1 as a prognostic indicator and a therapeutic target in renal cell carcinoma. Sci Rep. 2019;9:1-10.
  • [7] Liu YH, Li YL, Shen HT, Chien PJ, Sheu GT, Wang BY, et al. L-type amino acid transporter 1 regulates cancer stemness and the expression of programmed cell death 1 ligand 1 in lung cancer cells. Int J Mol Sci. 2021;22:10955 .
  • [8] Dickens D, Chiduza GN, Wright GSA, Pirmohamed M, Antonyuk S v., Hasnain SS. Modulation of LAT1 (SLC7A5) transporter activity and stability by membrane cholesterol. Sci Rep. 2017;7:1-13.
  • [9] Detta A, Cruickshank GS. L-Amino Acid Transporter-1 and Boronophenylalanine-Based Boron Neutron Capture Therapy of Human Brain Tumors. Cancer Res. 2009;69:2126-32.
  • [10] Shimizu A, Kaira K, Kato M, Yasuda M, Takahashi A, Tominaga H, et al. Prognostic significance of L-type amino acid transporter 1 (LAT1) expression in cutaneous melanoma. Melanoma Res. 2015;25(5):399-405.
  • [11] Cascio L, Chen CF, Pauly R, Srikanth S, Jones K, Skinner CD, et al. Abnormalities in the genes that encode Large Amino Acid Transporters increase the risk of Autism Spectrum Disorder. Mol Genet Genomic Med. 2020;8:1-12.
  • [12] Scala I, Concolino D, Nastasi A, Esposito G, Crisci D, Sestito S, et al. Beneficial effects of slow-release large neutral amino acids after a phenylalanine oral load in patients with phenylketonuria. Nutrients. 2021;13:4012.
  • [13] Krause G, Hinz KM. Thyroid hormone transport across L-type amino acid transporters: What can molecular modelling tell us? Mol Cell Endocrinol. 2017 Dec 15;458:68-75.
  • [14] SLC7A8 - Large neutral amino acids transporter small subunit 2 - Homo sapiens (Human) | UniProtKB | UniProt.
  • [15] SLC43A1 - Large neutral amino acids transporter small subunit 3 - Homo sapiens (Human) | UniProtKB | UniProt.
  • [16] Nedunchezhian K, Aswath N, Thiruppathy M, Thirugnanamurthy S. Boron neutron capture therapy - a literature review. Journal of Clinical and Diagnostic Research. 2016;10:ZE01-4.
  • [17] Silarski M, Dziedzic-Kocurek K, Szczepanek M. Combined BNCT and PET for theranostics. BioAlgorithms and Med-Systems. 2021;17:293-300.
  • [18] Dymova MA, Taskaev SY, Richter VA, Kuligina EV. Boron neutron capture therapy: Current status and future perspectives. Cancer Commun. 2020;40:406-21.
  • [19] Brown K, Mountford MH, Allen BJ, Mishima Y, Ichihashi M, Parsons P. Neutron Irradiation of Human Melanoma Cells. Pigment Cell Res. 1989;2(4):319-24.
  • [20] Wongthai P, Hagiwara K, Miyoshi Y, Wiriyasermkul P, Wei L, Ohgaki R, et al. Boronophenylalanine, a boron delivery agent for boron neutron capture therapy, is transported by ATB0,+, LAT1 and LAT2. Cancer Sci. 2015;106:279-86.
  • [21] Kubicz E, Stępień E. Results Transcriptomes Sequencing Dataset for Human Melanoma and Melanocytes Cell Cultures. Kraków : Repozytorium Uniwersytetu Jagiellońskiego, 2021. https://doi.org/10.26106/y8e9-7603.
  • [22] Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):1-21.
  • [23] Maza E, Frasse P, Senin P, Bouzayen M, Zouine M. Comparison of normalization methods for differential gene expression analysis in RNA-Seq experiments: A matter of relative size of studied transcriptomes. Commun Integr Biol. 2013;6(6).
  • [24] Evans C, Hardin J, Stoebel DM. Selecting betweensample RNA-Seq normalization methods from the perspective of their assumptions. Brief Bioinform. 2018;19(5):776-92.
  • [25] Chen SY, Feng Z, Yi X. A general introduction to adjustment for multiple comparisons. J Thorac Dis. 2017;9(6):1725-9.
  • [26] Herlyn M, Balaban G, Bennicelli J, Guerry IV D, Halaban R, Elder DE, et al. Primary melanoma cells of the vertical growth phase: Similarities to metastatic cells. J Natl Cancer Inst. 1985;74:283-9.
  • [27] Kubicz E. Biomedical applications of Positron Annihilation Lifetime Spectroscopy: nanostructural characterization of normal and cancer cells and tissues [Ph.D. thesis]. Kraków, Jagiellonian University; 2020.
  • [28] Uhlen M, Zhang C, Lee S, Sjöstedt E, Fagerberg L, Bidkhori G, et al. A pathology atlas of the human cancer transcriptome. Science. 2017;357:eaan2507.
  • [29] Expression of LAT2 in melanoma - The Human Protein Atlas. Available from: https://www.proteinatlas.org/ENSG00000086730- LAT2/pathology/melanoma.
Uwagi
Opublikowane przez Sciendo. Opracowanie rekordu ze środków MEiN, umowa nr SONP/SP/546092/2022 w ramach programu "Społeczna odpowiedzialność nauki" - moduł: Popularyzacja nauki i promocja sportu (2022-2023).
Typ dokumentu
Bibliografia
Identyfikator YADDA
bwmeta1.element.baztech-9f1eb79e-429a-4467-855f-cb672671793c
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