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Research Paper

Obesity enriches for tumor protective microbial metabolites and treatment refractory cells to confer therapy resistance in PDAC

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Article: 2096328 | Received 29 Oct 2021, Accepted 20 Jun 2022, Published online: 11 Jul 2022

References

  • Pothuraju R, Rachagani S, Junker WM, Chaudhary S, Saraswathi V, Kaur S, Batra SK. Pancreatic cancer associated with obesity and diabetes: an alternative approach for its targeting. J Exp Clin Cancer Res. 2018;37:319. doi:10.1186/s13046-018-0963-4.
  • Cascetta P, Cavaliere A, Piro G, Torroni L, Santoro R, Tortora G, Melisi D, Carbone C. Pancreatic cancer and obesity: molecular mechanisms of cell transformation and chemoresistance. Int J Mol Sci. 2018;19:3331. doi:10.3390/ijms19113331.
  • Rawla P, Thandra KC, Sunkara T. Pancreatic cancer and obesity: epidemiology, mechanism, and preventive strategies. Clin J Gastroenterol. 2019;12:285–18. doi:10.1007/s12328-019-00953-3.
  • Genkinger JM, Spiegelman D, Anderson KE, Bernstein L, van den Brandt PA, Calle EE, English DR, Folsom AR, Freudenheim JL, Fuchs CS, et al. A pooled analysis of 14 cohort studies of anthropometric factors and pancreatic cancer risk. Int J Cancer. 2011;129:1708–1717. doi:10.1002/ijc.25794.
  • McWilliams RR, Matsumoto ME, Burch PA, Kim GP, Halfdanarson TR, de Andrade M, Reid-Lombardo K, Bamlet WR. Obesity adversely affects survival in pancreatic cancer patients. Cancer. 2010;116:5054–5062. doi:10.1002/cncr.25465.
  • Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348:1625–1638. doi:10.1056/NEJMoa021423.
  • Li D, Morris JS, Liu J, Hassan MM, Day RS, Bondy ML, Abbruzzese JL. Body mass index and risk, age of onset, and survival in patients with pancreatic cancer. JAMA. 2009;301:2553–2562. doi:10.1001/jama.2009.886.
  • Cani PD, Jordan BF. Gut microbiota-mediated inflammation in obesity: a link with gastrointestinal cancer. Nat Rev Gastroenterol Hepatol. 2018;15:671–682. doi:10.1038/s41575-018-0025-6.
  • Mendez R, Kesh K, Arora N, Di Martino L, McAllister F, Merchant N, Banerjee S, Banerjee S. Microbial dysbiosis and polyamine metabolism as predictive markers for early detection of pancreatic cancer. Carcinogenesis. 2020;41:561–570. doi:10.1093/carcin/bgz116.
  • Zheng Y, Wang T, Tu X, Huang Y, Zhang H, Tan D, Jiang W, Cai S, Zhao P, Song R, et al. Gut microbiome affects the response to anti-PD-1 immunotherapy in patients with hepatocellular carcinoma. J Immunother Cancer. 2019;7:193. doi:10.1186/s40425-019-0650-9.
  • Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillere R, Fluckiger A, Messaoudene M, Rauber C, Roberti MP, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018;359:91–97. doi:10.1126/science.aan3706.
  • Mima K, Nakagawa S, Sawayama H, Ishimoto T, Imai K, Iwatsuki M, Hashimoto D, Baba Y, Yamashita Y-I, Yoshida N, et al. The microbiome and hepatobiliary-pancreatic cancers. Cancer Lett. 2017;402:9–15. doi:10.1016/j.canlet.2017.05.001.
  • Kesh K, Mendez R, Abdelrahman L, Banerjee S, Banerjee S. Type 2 diabetes induced microbiome dysbiosis is associated with therapy resistance in pancreatic adenocarcinoma. Microb Cell Fact. 2020;19:75. doi:10.1186/s12934-020-01330-3.
  • Geller LT, Barzily-Rokni M, Danino T, Jonas OH, Shental N, Nejman D, Gavert N, Zwang Y, Cooper ZA, Shee K, et al. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science. 2017;357:1156–1160. doi:10.1126/science.aah5043.
  • Tsvetikova SA, Koshel EI. Microbiota and cancer: host cellular mechanisms activated by gut microbial metabolites. Int J Med Microbiol. 2020;310:151425. doi:10.1016/j.ijmm.2020.151425.
  • Cueva C, Silva M, Pinillos I, Bartolome B, Moreno-Arribas MV. Interplay between dietary polyphenols and oral and gut microbiota in the development of colorectal cancer. Nutrients. 2020;12:625. doi:10.3390/nu12030625.
  • Elinav E, Garrett WS, Trinchieri G, Wargo J. The cancer microbiome. Nat Rev Cancer. 2019;19:371–376. doi:10.1038/s41568-019-0155-3.
  • Mehdi A, Attias M, Mahmood N, Arakelian A, Mihalcioiu C, Piccirillo CA, Szyf M, Rabbani SA. Enhanced anticancer effect of a combination of S-adenosylmethionine (SAM) and immune checkpoint inhibitor (ICPi) in a syngeneic mouse model of advanced melanoma. Front Oncol. 2020;10:1361. doi:10.3389/fonc.2020.01361.
  • Mahmood N, Arakelian A, Cheishvili D, Szyf M, Rabbani SA. S-adenosylmethionine in combination with decitabine shows enhanced anti-cancer effects in repressing breast cancer growth and metastasis. J Cell Mol Med. 2020;24:10322–10337. doi:10.1111/jcmm.15642.
  • Morris RC, Elliott MS. Queuosine modification of tRNA: a case for convergent evolution. Mol Genet Metab. 2001;74:147–159. doi:10.1006/mgme.2001.3216.
  • Slany RK, Kersten H. Genes, enzymes and coenzymes of queuosine biosynthesis in procaryotes. Biochimie. 1994;76:1178–1182. doi:10.1016/0300-9084(94)90047-7.
  • Tuorto F, Legrand C, Cirzi C, Federico G, Liebers R, Muller M, Ehrenhofer‐Murray AE, Dittmar G, Gröne H-J, Lyko F, et al. Queuosine-modified tRNAs confer nutritional control of protein translation. EMBO J. 2018;37. doi:10.15252/embj.201899777.
  • Bao B, Teslow EA, Mitrea C, Boerner JL, Dyson G, Bollig-Fischer A. Role of TET1 and 5hmC in an obesity-linked pathway driving cancer stem cells in triple-negative breast cancer. Mol Cancer Res. 2020;18:1803–1814. doi:10.1158/1541-7786.MCR-20-0359.
  • Huang H, Wang Y, Kandpal M, Zhao G, Cardenas H, Ji Y, Chaparala A, Tanner EJ, Chen J, Davuluri RV, et al. FTO-dependent N 6 -methyladenosine modifications inhibit ovarian cancer stem cell self-renewal by blocking cAMP signaling. Cancer Res. 2020;80:3200–3214. doi:10.1158/0008-5472.CAN-19-4044.
  • Kesh K, Garrido VT, Dosch A, Durden B, Gupta VK, Sharma NS, Lyle M, Nagathihalli N, Merchant N, Saluja A, et al. Stroma secreted IL6 selects for “stem-like” population and alters pancreatic tumor microenvironment by reprogramming metabolic pathways. Cell Death Dis. 2020;11:967. doi:10.1038/s41419-020-03168-4.
  • Hayashi T, Fujita K, Nojima S, Hayashi Y, Nakano K, Ishizuya Y, Wang C, Yamamoto Y, Kinouchi T, Matsuzaki K, et al. High-fat diet-induced inflammation accelerates prostate cancer growth via IL6 signaling. Clin Cancer Res. 2018;24:4309–4318. doi:10.1158/1078-0432.CCR-18-0106.
  • Wunderlich CM, Ackermann PJ, Ostermann AL, Adams-Quack P, Vogt MC, Tran ML, Nikolajev A, Waisman A, Garbers C, Theurich S, et al. Obesity exacerbates colitis-associated cancer via IL-6-regulated macrophage polarisation and CCL-20/CCR-6-mediated lymphocyte recruitment. Nat Commun. 2018;9:1646. doi:10.1038/s41467-018-03773-0.
  • Caspi R, Billington R, Keseler IM, Kothari A, Krummenacker M, Midford PE, Ong WK, Paley S, Subhraveti P, Karp PD, et al. The MetaCyc database of metabolic pathways and enzymes - a 2019 update. Nucleic Acids Res. 2020;48:D445–D53. doi:10.1093/nar/gkz862.
  • Pathak C, Jaiswal YK, Vinayak M. Queuine promotes antioxidant defence system by activating cellular antioxidant enzyme activities in cancer. Biosci Rep. 2008;28:73–81. doi:10.1042/BSR20070011.
  • Iyengar NM, Gucalp A, Dannenberg AJ, Hudis CA. Obesity and cancer mechanisms: tumor microenvironment and inflammation. J Clin Oncol. 2016;34:4270–4276. doi:10.1200/JCO.2016.67.4283.
  • Gupta VK, Sharma NS, Kesh K, Dauer P, Nomura A, Giri B, Dudeja V, Banerjee S, Bhattacharya S, Saluja A, et al. Metastasis and chemoresistance in CD133 expressing pancreatic cancer cells are dependent on their lipid raft integrity. Cancer Lett. 2018;439:101–112. doi:10.1016/j.canlet.2018.09.028.
  • Nomura A, Dauer P, Gupta V, McGinn O, Arora N, Majumdar K, Iii CU, Dalluge J, Dudeja V, Saluja A, et al. Microenvironment mediated alterations to metabolic pathways confer increased chemo-resistance in CD133+ tumor initiating cells. Oncotarget. 2016;7:56324–56337. doi:10.18632/oncotarget.10838.
  • Bae S, Ulrich CM, Neuhouser ML, Malysheva O, Bailey LB, Xiao L, Brown EC, Cushing-Haugen KL, Zheng Y, Cheng TYD, et al. Plasma choline metabolites and colorectal cancer risk in the Women’s Health Initiative Observational Study. Cancer Res. 2014;74:7442–7452. doi:10.1158/0008-5472.CAN-14-1835.
  • Oellgaard J, Winther SA, Hansen TS, Rossing P, von Scholten BJ. Trimethylamine N-oxide (TMAO) as a new potential therapeutic target for insulin resistance and cancer. Curr Pharm Des. 2017;23:3699–3712. doi:10.2174/1381612823666170622095324.
  • Fergus C, Barnes D, Alqasem MA, Kelly VP. The queuine micronutrient: charting a course from microbe to man. Nutrients. 2015;7:2897–2929. doi:10.3390/nu7042897.
  • Reisser T, Langgut W, Kersten H. The nutrient factor queuine protects HeLa cells from hypoxic stress and improves metabolic adaptation to oxygen availability. Eur J Biochem. 1994;221:979–986. doi:10.1111/j.1432-1033.1994.tb18814.x.
  • Langgut W, Kersten H. The deazaguanine-derivative, queuine, affects cell proliferation, protein phosphorylation and the expression of the proto oncogenes c-fos and c-myc in HeLa cells. FEBS Lett. 1990;265:33–36. doi:10.1016/0014-5793(90)80877-L.
  • Langgut W, Reisser T, Nishimura S, Kersten H. Modulation of mammalian cell proliferation by a modified tRNA base of bacterial origin. FEBS Lett. 1993;336:137–142. doi:10.1016/0014-5793(93)81627-C.
  • Pathak C, Vinayak M. Modulation of lactate dehydrogenase isozymes by modified base queuine. Mol Biol Rep. 2005;32:191–196. doi:10.1007/s11033-004-6941-2.
  • Nishimura S. Structure, biosynthesis, and function of queuosine in transfer RNA. Prog Nucleic Acid Res Mol Biol. 1983;28:49–73.
  • Langgut W, Reisser T, Kersten H. Queuine modulates growth of HeLa cells depending on oxygen availability. Biofactors. 1990;2:245–249.
  • Caballero VC, Toledo VP, Maturana C, Fisher CR, Payne SM, Salazar JC. Expression of Shigella flexneri gluQ-rs gene is linked to dksA and controlled by a transcriptional terminator. BMC Microbiol. 2012;12:226. doi:10.1186/1471-2180-12-226.
  • Salazar JC, Ambrogelly A, Crain PF, McCloskey JA, Soll D. A truncated aminoacyl-tRNA synthetase modifies RNA. Proc Natl Acad Sci U S A. 2004;101:7536–7541. doi:10.1073/pnas.0401982101.
  • Dubois DY, Blaise M, Becker HD, Campanacci V, Keith G, Giege R, Cambillau C, Lapointe J, Kern D. An aminoacyl-tRNA synthetase-like protein encoded by the Escherichia coli yadB gene glutamylates specifically tRNA Asp. Proc Natl Acad Sci U S A. 2004;101:7530–7535. doi:10.1073/pnas.0401634101.
  • Luo J, Li YN, Wang F, Zhang WM, Geng X. S-adenosylmethionine inhibits the growth of cancer cells by reversing the hypomethylation status of c-myc and H-ras in human gastric cancer and colon cancer. Int J Biol Sci. 2010;6:784–795. doi:10.7150/ijbs.6.784.
  • Ilisso CP, Castellano M, Zappavigna S, Lombardi A, Vitale G, Dicitore A, Cacciapuoti G, Caraglia M, Porcelli M. The methyl donor S-adenosylmethionine potentiates doxorubicin effects on apoptosis of hormone-dependent breast cancer cell lines. Endocrine. 2015;50:212–222. doi:10.1007/s12020-014-0484-7.
  • Treangen TJ, Koren S, Sommer DD, Liu B, Astrovskaya I, Ondov B, Darling AE, Phillippy AM, Pop M. MetAMOS: a modular and open source metagenomic assembly and analysis pipeline. Genome Biol. 2013;14:R2. doi:10.1186/gb-2013-14-1-r2.
  • Robertson CE, Harris JK, Wagner BD, Granger D, Browne K, Tatem B, Feazel LM, Park K, Pace NR, Frank DN, et al. Explicet: graphical user interface software for metadata-driven management, analysis and visualization of microbiome data. Bioinformatics. 2013;29:3100–3101. doi:10.1093/bioinformatics/btt526.
  • Abubucker S, Segata N, Goll J, Schubert AM, Izard J, Cantarel BL, Rodriguez-Mueller B, Zucker J, Thiagarajan M, Henrissat B, et al. Metabolic reconstruction for metagenomic data and its application to the human microbiome. PLoS Comput Biol. 2012;8:e1002358. doi:10.1371/journal.pcbi.1002358.
  • Mendez R, Del Carmen Piqueras M, Raskind A, de Jong FA, Beecher C, Bhattacharya SK, Banerjee S. Quantitative metabolomics using isotope residue outlier analysis (IROA((R))) with internal standards. Methods Mol Biol. 2019;1996:41–46.