{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:42:59Z","timestamp":1760143379032,"version":"build-2065373602"},"reference-count":29,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T00:00:00Z","timestamp":1706832000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Mexican Council of Humanities Sciences and Technologies (CONAHCyT)","doi-asserted-by":"publisher","award":["682133"],"award-info":[{"award-number":["682133"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Solid tumors frequently present a heterogeneous tumor microenvironment. Because tumors have the potential to proliferate quickly, the consequence is a reduction in the nutrients, a reduction in the pH (&lt;6.8), and a hypoxic environment. Although it is often assumed that tumor clones show a similar growth rate with little variations in nutrient consumption, the present study shows how growth-specific rate (\u00b5), the specific rates of glucose, lactate, and glutamine consumption (qS), and the specific rates of lactate and glutamate production (qP) of 2D-cultured lung tumor cells are affected by changes in their environment. We determined in lung tumor cells (A427, A549, Calu-1, and SKMES-1) the above mentioned kinetic parameters during the exponential phase under different culture conditions, varying the predominant carbon source, pH, and oxygen tension. MCF-7 cells, a breast tumor cell line that can consume lactate, and non-transformed fibroblast cells (MRC-5) were included as controls. We also analyzed how cell-cycle progression and the amino acid transporter CD98 expression were affected. Our results show that: (1) In glucose presence, \u03bc increased, but qS Glucose and qP Lactate decreased when tumor cells were cultured under acidosis as opposed to neutral conditions; (2) most lung cancer cell lines consumed lactate under normoxia or hypoxia; (3) although qS Glutamine diminished under hypoxia or acidosis, it slightly increased in lactate presence, a finding that was associated with CD98 upregulation; and (4) under acidosis, G0\/G1 arrest was induced in A427 cancer cells, although this phenomenon was significantly increased when glucose was changed by lactate as the predominant carbon-source. Hence, our results provide an understanding of metabolic responses that tumor cells develop to survive under stressful conditions, providing clues for developing promising opportunities to improve traditional cancer therapies.<\/jats:p>","DOI":"10.3390\/metabo14020103","type":"journal-article","created":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T09:24:08Z","timestamp":1706865848000},"page":"103","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Metabolic Responses of Lung Adenocarcinoma Cells to Survive under Stressful Conditions Associated with Tumor Microenvironment"],"prefix":"10.3390","volume":"14","author":[{"given":"Angeles","family":"Carlos-Reyes","sequence":"first","affiliation":[{"name":"Laboratorio de Onco-Inmunobiologia, Departamento de Enfermedades Cr\u00f3nico-Degenerativas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susana","family":"Romero-Garcia","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4932-3244","authenticated-orcid":false,"given":"Heriberto","family":"Prado-Garcia","sequence":"additional","affiliation":[{"name":"Laboratorio de Onco-Inmunobiologia, Departamento de Enfermedades Cr\u00f3nico-Degenerativas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of Cancer: New Dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: The metabolic requirements of cell proliferation","volume":"324","author":"Cantley","year":"2009","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1126\/science.123.3191.309","article-title":"On the origin of cancer cells","volume":"123","author":"Warburg","year":"1956","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Riemann, A., Schneider, B., Ihling, A., Nowak, M., Sauvant, C., Thews, O., and Gekle, M. 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