Markers of mitochondrial metabolism in tumor hypoxia, systemic inflammation, and adverse outcome of rectal cancer
| Autor: | Svein Dueland, Ying Esbensen, Anne Hansen Ree, Therese Seierstad, Kjersti Flatmark, Paula A. Bousquet, Tone Frost Bathen, Sebastian Meltzer, Kathrine Røe Redalen, Beathe Sitter, Linda Sønstevold, Lars Eide |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Original article Cancer Research Colorectal cancer Inflammation Systemic inflammation lcsh:RC254-282 03 medical and health sciences 0302 clinical medicine Carcinoembryonic antigen medicine biology Tumor hypoxia business.industry Hypoxia (medical) lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Primary tumor 030104 developmental biology Oncology 030220 oncology & carcinogenesis biology.protein Cancer research Tumor necrosis factor alpha medicine.symptom business |
| Zdroj: | Translational Oncology Translational Oncology, Vol 12, Iss 1, Pp 76-83 (2019) |
| ISSN: | 1936-5233 |
| Popis: | Tumor hypoxia contributes to therapy resistance and metastatic progression of locally advanced rectal cancer (LARC). We postulated that the tumor mitochondrial metabolism, manifested by reactive oxygen species (ROS) and mitochondrial DNA (mtDNA) damage, reflects how hypoxic conditions connect to cancer-induced systemic inflammation and poor outcome. Levels of ROS and mtDNA damage were analyzed in three colorectal cancer (CRC) cell lines cultured for 24 hours under normoxia (21% O2) or hypoxia (0.2% O2) and serum sampled at the time of diagnosis from 35 LARC patients participating in a prospective therapy study. Compared with normoxia, ROS were significantly repressed and mtDNA damage was significantly enhanced in the hypoxic CRC cell lines; hence, a low ratio of ROS to mtDNA damage was an indicator of hypoxic conditions. In the LARC patients, low serum ROS were associated with elevated levels of circulating carcinoembryonic antigen and tumor choline concentration, both indicative of unfavorable biology, as well as adverse progression-free and overall survival. A low ratio of ROS to mtDNA damage in serum was associated with poor local tumor response to the neoadjuvant treatment and, of note, elevated systemic inflammation factors (C-reactive protein, the interleukin-1 receptor antagonist, and factors involved in tumor necrosis factor signaling), indicating that deficient treatment response locally and detrimental inflammation systemically link to a hypoxic mitochondrial metabolism. In conclusion, serum ROS and damaged mtDNA may be markers of the mitochondrial metabolism driven by the state of oxygenation of the primary tumor and possibly implicated in systemic inflammation and adverse outcome of LARC. © 2018 The Authors. Published by Elsevier Inc. on behalf of Neoplasia Press, Inc. Thisis an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Databáze: | OpenAIRE |
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