Biopolym. Cell. 2019; 35(4):313-320.
http://dx.doi.org/10.7124/bc.000A0D
Molecular Biomedicine
Expression pattern of immune- and cancer-associated genes in peripheral blood of mice bearing melanoma cells
1Gerashchenko G. V., 1Vagina I. M., 1Vagin Yu. V., 1Tkachuk Z. Yu., 1Kashuba V. I.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03143

Abstract

Aim. To identify putative non-invasive expression markers, based on relative expression (RE) of cancer- and immune-associated genes, in peripheral blood of mice, bearing melanoma cells. Methods. RE of 56 cancer- and immune-associated genes was assessed byquantitative PCR in peripheral blood of C57BL/6j mice inoculated with B16 mouse melanoma cells and in control animals. Results. Eleven genes showed significant differences in the RE levels in mice,bearing melanoma: six genes (Ccl5, Il1b, Mif, Rnasel, S100a1 and Tgfb1) were expressed at higher levels, and five genes (Erbb2, Ifnb1, Il6, Pdcd1 and Prom1) were downregulated in comparison with the control animals. We have demonstrated a stable immunosuppressed state of mice inoculated with melanoma cells as evidenced by decreased RE levels of Ifnb1 and Pdcd1 and increased RE levels of Lbp, Tlr3, Tlr8, Gstp1, Prom1, Oas1a, Oas3 and Il1b. Conclusions. Assessment of expression of cancer- and immune-associated genes in peripheral blood during growth of malignant cells in experimental animals may result in discovery of effective noninvasive expression markers for the prognosis of the cancer outcome and chemotherapy efficiency
Keywords: melanoma, relative gene expression, immune-associated genes, putative expression markers.
Full text: (PDF, in English)

References

[1] Bastian BC. The molecular pathology of melanoma: an integrated taxonomy of melanocytic neoplasia. Annu Rev Pathol. 2014;9:239-271.
[2] Bommareddy PK, Silk AW, Kaufman HL. Intratumoral Approaches for the Treatment of Melanoma. Cancer J. 201, 23(1):40-47.
[3] Ma J, Guo W, Li C. Ubiquitination in melanoma pathogenesis and treatment.Cancer Med. 2017, 6(6):1362-1377.
[4] Tímár J, Hársing J, Somlai B. Molecular classification and markers ofmalignant melanoma. Magy Onkol. 2013, 57(2):73-78.
[5] Eriksson J, Le Joncour V, Nummela P, Jahkola T, Virolainen S, Laakkonen P, Saksela O, Hölttä E. Gene expression analyses of primary melanomas reveal CTHRC1 as an important player in melanoma progression. Oncotarget. 2016,7(12):15065-15092.
[6] Metri R, Mohan A, Nsengimana J, Pozniak J, Molina-Paris C, Newton-Bishop J, Bishop D, Chandra N. Identification of a gene signature for discriminatingmetastatic from primary melanoma using a molecular interaction network approach. Sci Rep. 2017,7(1):17314.
[7] Melnichuk N, Kashuba V, Rybalko S, Tkachuk Z. Complexes ofOligoribonucleotides with d-Mannitol Modulate the Innate Immune Response toInfluenza A Virus H1N1 (A/FM/1/47) In Vivo. Pharmaceuticals (Basel). 2018,11(3). pii: E73.
[8] Gerashchenko GV, Mankovska OS, Dmitriev AA, Mevs LV, Rosenberg EE, Pikul MV, Marynychenko MV, Gryzodub OP, Stakhovsky EO, Kashuba VI. Expression of epithelial-mesenchymal transition-related genes in prostate tumours. Biopolym. Cell. 2017,33(5):335-355.
[9] Gerashchenko GV, Grygoruk OV, Kononenko OA, Gryzodub OP, Stakhovsky EO, Kashuba VI. Expression pattern of genes associated with tumor microenvironment in prostate cancer. Exp Oncol. 2018, 40(4):315-322.
[10] Gerashchenko GV, Kononenko OA, Bondarenko YuM, Stakhovsky EO, Kashuba VI. Expression patterns of genes that regulate lipid metabolism in prostate tumors. Biopolym. Cell. 2018,34(6):445-460.
[11] Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. Journal of the Royal Statistical Society. 1995, 57: 289-300.
[12] García de Guadiana-Romualdo L, Español-Morales I, Cerezuela-Fuentes P, Consuegra-Sánchez L, Hernando-Holgado A, Esteban-Torrella P, Jiménez-Santos E, Viqueira-González M, de Béjar-Almira Á, Albaladejo-Otón MD. Value oflipopolysaccharide binding protein as diagnostic marker of infection in adultcancer patients with febrile neutropenia: comparison with C-reactive protein,procalcitonin, and interleukin 6. Support Care Cancer. 2015, 23(7):2175-2182.
[13] Fan Y, Yang L, Wei Q, Ding Y, Tang Z, Tan P, Lin T, Guo D, Qiu S. Toll-likereceptor 10 (TLR10) exhibits suppressive effects on inflammation of prostateepithelial cells. Asian J Androl. 2019, Jan 1. doi: 10.4103/aja.aja_100_18.
[14] Grimmig T, Matthes N, Hoeland K, Tripathi S, Chandraker A, Grimm M, Moench R, Moll EM, Friess H, Tsaur I, Blaheta RA, Germer CT, Waaga-Gasser AM, Gasser M.TLR7 and TLR8 expression increases tumor cell proliferation and promoteschemoresistance in human pancreatic cancer. Int J Oncol. 2015, 47(3):857-866.
[15] Bugge M, Bergstrom B, Eide OK, Solli H, Kjønstad IF, Stenvik J, Espevik T, Nilsen NJ. Surface Toll-like receptor 3 expression in metastatic intestinalepithelial cells induces inflammatory cytokine production and promotesinvasiveness. J Biol Chem. 2017, 292(37):15408-15425.
[16] Ding Q, Lu P, Xia Y, Ding S, Fan Y, Li X, Han P, Liu J, Tian D, Liu M. CXCL9: evidence and contradictions for its role in tumor progression. Cancer Med. 2016,5(11):3246-3259.
[17] Tokunaga R, Zhang W, Naseem M, Puccini A, Berger MD, Soni S, McSkane M, Baba H, Lenz HJ. CXCL9, CXCL10, CXCL11/CXCR3 axis for immune activation - A target fornovel cancer therapy. Cancer Treat Rev. 2018, 63:40-47.
[18] Choi UY, Kang JS, Hwang YS, Kim YJ. Oligoadenylate synthase-like (OASL) proteins: dual functions and associations with diseases. Exp Mol Med. 2015, 47:e144.
[19] BanerjeeS, GushoE, GaughanC, DongB, GuX, Holvey-BatesE, TalukdarM, LiY, WeissSR, SicheriF, SaunthararajahY, StarkGR, SilvermanRH.OAS-RNase L innate immune pathway mediates the cytotoxicity of a DNA-demethylating drug. Proc Natl AcadSci U S A. 2019, 116(11):5071-5076.
[20] Cheah MT, Chen JY, Sahoo D, Contreras-Trujillo H, Volkmer AK, Scheeren FA, Volkmer JP, Weissman IL. CD14-expressing cancer cells establish the inflammatory and proliferative tumor microenvironment in bladder cancer. Proc Natl AcadSci U S A. 2015, 112(15):4725-4730.
[21] Turrini R, Pabois A, Xenarios I, Coukos G, Delaloye JF, Doucey MA. TIE-2expressing monocytes in human cancers. Oncoimmunology. 2017, 6(4):e1303585.
[22] Mutallip M, Nohata N, Hanazawa T, Kikkawa N, Horiguchi S, Fujimura L, KawakamiK, Chiyomaru T, Enokida H, Nakagawa M, Okamoto Y, Seki N. GlutathioneS-transferase P1 suppresses cell apoptosis and its regulation by miR-133αin head and neck squamous cell carcinoma (HNSCC). Int J Mol Med. 2011, 27(3):345-352.
[23] MiyanishiK, TakayamaT, OhiM, HayashiT, NobuokaA, NakajimaT, TakimotoR, KogawaK, KatoJ, SakamakiS, NiitsuY.GlutathioneS-transferase-pioverexpressioniscloselyassociatedwithK-rasmutationduringhumancoloncarcinogenesis. Gastroenterology. 2001, 121(4):865-874.
[24] Ruzza P, Rosato A, Rossi CR, Floreani M, Quintieri L. Glutathione transferases as targets for cancer therapy. Anticancer Agents Med Chem. 2009, 9(7):763-777.
[25] Di Pietro G, Magno LA, Rios-Santos F. Glutathione S-transferases: an overview in cancer research. Expert Opin Drug MetabToxicol. 2010, 6(2):153-170.
[26] Louie SM, Grossman EA, Crawford LA, Ding L, Camarda R, Huffman TR, Miyamoto DK, Goga A, Weerapana E, Nomura DK. GSTP1 Is a Driver of Triple-Negative BreastCancer Cell Metabolism and Pathogenicity. Cell Chem Biol. 2016,23(5):567-578.
[27] Qiu ZX, Zhao S, Mo XM, Li WM. Overexpression of PROM1 (CD133) confers poor prognosis in non-small cell lung cancer. Int J ClinExpPathol. 2015, 8(6):6589-6595.
[28] Ren F, Sheng WQ, Du X. CD133: a cancer stem cells marker, is used in colorectal cancers. World J Gastroenterol. 2013, 19(17):2603-2611.
[29] Kashihara H, Shimada M, Kurita N, Iwata T, Sato H, Kozo Yoshikawa, Higashijima J, Chikakiyo M, Nishi M, Matsumoto N. CD133 expression is correlated with poor prognosis in colorectal cancer. Hepatogastroenterology. 2014, 61(134):1563-7.
[30] Guo B, Fu S, Zhang J, Liu B, Li Z. Targeting inflammasome/IL-1 pathways forcancer immunotherapy. Sci Rep. 2016, 6:36107.
[31] Tulotta C, Ottewell P. The role of IL-1B in breast cancer bone metastasis. EndocrRelat Cancer. 2018, 25(7):R421-R434.
[32] Müller L, Aigner P, Stoiber D. Type I Interferons and Natural Killer Cell Regulation in Cancer. Front Immunol. 2017, 8:304.
[33] Karachaliou N, Gonzalez-Cao M, Crespo G, Drozdowskyj A, Aldeguer E, Gimenez-Capitan A, Teixido C, Molina-Vila MA, Viteri S, De Los Llanos Gil M, Algarra SM, Perez-Ruiz E, Marquez-Rodas I, Rodriguez-Abreu D, Blanco R, Puertolas T, Royo MA, Rosell R. Interferon gamma, an important marker of response to immune checkpoint blockade in non-small cell lung cancer and melanoma patients. TherAdv Med Oncol.2018, 10:17588340-17749748.