Next Article in Journal
Mouse Liver Compensates Loss of Sgpl1 by Secretion of Sphingolipids into Blood and Bile
Previous Article in Journal
Selected Biomarkers of Tick-Borne Encephalitis: A Review
Previous Article in Special Issue
Applying Proteomics and Integrative “Omics” Strategies to Decipher the Chronic Kidney Disease-Related Atherosclerosis
Article

Monocarboxylate Transporter-2 Expression Restricts Tumor Growth in a Murine Model of Lung Cancer: A Multi-Omic Analysis

1
Department of Child Health and the Child Health Research Institute, School of Medicine, University of Missouri, Columbia, MO 65201, USA
2
Department of Ophthalmology, School of Medicine, University of Missouri, Mizzou, Columbia, MO 65212, USA
3
Institute for Data Science and Informatics, Department of Electrical Engineering and Computer Science, University of Missouri, Columbia, MO 64110, USA
4
Department of Veterinary Pathobiology and Metagenomics Core, University of Missouri, Columbia, MO 65212, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: Amedeo Amedei
Int. J. Mol. Sci. 2021, 22(19), 10616; https://doi.org/10.3390/ijms221910616
Received: 16 August 2021 / Revised: 27 September 2021 / Accepted: 27 September 2021 / Published: 30 September 2021
(This article belongs to the Special Issue OMICS for Metabolic Mysfunctions)
Monocarboxylate transporter 2 (MCT2) is a major high-affinity pyruvate transporter encoded by the SLC16A7 gene, and is associated with glucose metabolism and cancer. Changes in the gut microbiota and host immune system are associated with many diseases, including cancer. Using conditionally expressed MCT2 in mice and the TC1 lung carcinoma model, we examined the effects of MCT2 on lung cancer tumor growth and local invasion, while also evaluating potential effects on fecal microbiome, plasma metabolome, and bulk RNA-sequencing of tumor macrophages. Conditional MCT2 mice were generated in our laboratory using MCT2loxP mouse intercrossed with mCre-Tg mouse to generate MCT2loxP/loxP; Cre+ mouse (MCT2 KO). Male MCT2 KO mice (8 weeks old) were treated with tamoxifen (0.18 mg/g BW) KO or vehicle (CO), and then injected with mouse lung carcinoma TC1 cells (10 × 105/mouse) in the left flank. Body weight, tumor size and weight, and local tumor invasion were assessed. Fecal DNA samples were extracted using PowerFecal kits and bacterial 16S rRNA amplicons were also performed. Fecal and plasma samples were used for GC−MS Polar, as well as non-targeted UHPLC-MS/MS, and tumor-associated macrophages (TAMs) were subjected to bulk RNAseq. Tamoxifen-treated MCT2 KO mice showed significantly higher tumor weight and size, as well as evidence of local invasion beyond the capsule compared with the controls. PCoA and hierarchical clustering analyses of the fecal and plasma metabolomics, as well as microbiota, revealed a distinct separation between the two groups. KO TAMs showed distinct metabolic pathways including the Acetyl-coA metabolic process, activation of immune response, b-cell activation and differentiation, cAMP-mediated signaling, glucose and glutamate processes, and T-cell differentiation and response to oxidative stress. Multi-Omic approaches reveal a substantial role for MCT2 in the host response to TC1 lung carcinoma that may involve alterations in the gut and systemic metabolome, along with TAM-related metabolic pathway. These findings provide initial opportunities for potential delineation of oncometabolic immunomodulatory therapeutic approaches. View Full-Text
Keywords: MCT2; metabolome; microbiota; GC−MS; LCMS; tumor; lactate; RNA-seq; RNA MCT2; metabolome; microbiota; GC−MS; LCMS; tumor; lactate; RNA-seq; RNA
Show Figures

Figure 1

MDPI and ACS Style

Khalyfa, A.; Qiao, Z.; Raju, M.; Shyu, C.-R.; Coghill, L.; Ericsson, A.; Gozal, D. Monocarboxylate Transporter-2 Expression Restricts Tumor Growth in a Murine Model of Lung Cancer: A Multi-Omic Analysis. Int. J. Mol. Sci. 2021, 22, 10616. https://doi.org/10.3390/ijms221910616

AMA Style

Khalyfa A, Qiao Z, Raju M, Shyu C-R, Coghill L, Ericsson A, Gozal D. Monocarboxylate Transporter-2 Expression Restricts Tumor Growth in a Murine Model of Lung Cancer: A Multi-Omic Analysis. International Journal of Molecular Sciences. 2021; 22(19):10616. https://doi.org/10.3390/ijms221910616

Chicago/Turabian Style

Khalyfa, Abdelnaby, Zhuanhong Qiao, Murugesan Raju, Chi-Ren Shyu, Lyndon Coghill, Aaron Ericsson, and David Gozal. 2021. "Monocarboxylate Transporter-2 Expression Restricts Tumor Growth in a Murine Model of Lung Cancer: A Multi-Omic Analysis" International Journal of Molecular Sciences 22, no. 19: 10616. https://doi.org/10.3390/ijms221910616

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop