Date Published: June 26, 2019
Publisher: Public Library of Science
Author(s): Ludmiła Halczy-Kowalik, Arleta Drozd, Ewa Stachowska, Radosław Drozd, Tomasz Żabski, Wenancjusz Domagała, Juan J Loor.
Squamous cell carcinoma of the oral cavity mucosa grows under conditions of poor oxygenation and nutrient scarcity. Reprogramming of lipid biosynthesis accompanies tumor growth, but the conditions under which it occurs are not fully understood. The fatty acid content of the serum, tumor tissue and adjacent tumor microenvironment was measured by gas chromatography in 30 patients with squamous cell carcinoma grade 1–3. Twenty-five fatty acids were identified; their frequencies and percentages in each of the environments were assessed. Nineteen of the twenty-five fatty acids were found in tumor tissue, tumor adjacent tissue and blood serum. Of them, 8 were found in all thirty patients. Percentages of C16:0 and C18:1n9 were highest in the tumor, C18:1n9 and C16:0 were highest in tumor adjacent tissue, and C16:0 and C18:0 were highest in blood serum. The frequencies and amounts of C22:1n13, C22:4n6, C22:5n3 and C24:1 in tumor adjacent tissues were higher than those in blood serum, independent of the tumor grade. The correlations between the amount of fatty acid and tumor grade were the strongest in tumor adjacent tissues. The correlations between particular fatty acids were most prevalent for grade 1+2 tumors and were strongest for grade 3 tumors. In the adjacent tumor microenvironment, lipogenesis was controlled by C22:6w3. In blood serum, C18:1trans11 limited the synthesis of long-chain fatty acids. Our research reveals intensive lipid changes in oral cavity SCC adjacent to the tumor microenvironment and blood serum of the patients. Increase in percentage of some of the FAs in the path: blood serum–tumor adjacent microenvironment–tumor, and it is dependent on tumor grade. This dependency is the most visible in the tumor adjacent environment.
Primary squamous cell carcinoma (SCC), which originates in the mucosa of the oral cavity, develops via many non-lethal DNA disturbances in somatic cells that accumulate into a loss of control over cell proliferation, growth and differentiation. During the multiple stages of carcinogenesis, cells develop signals that increase proliferation and growth, prevent cell death and activate angiogenesis, invasion and metastasis. The functions described by Hanahan and Weinberg  might be found in the tumor microenvironment (TME) as a result of the reprogramming of energy metabolism and the avoidance of the immune response. Cancer cell development depends on the production of lipids that are necessary for cell membrane formation, protein modification and the transmission of oncogenic signals. Inhibition of lipogenesis by fatty acid synthase (FASN) inhibitors raises the possibility of limiting neoplasm development .
We obtained the approval of the Bioethical Committee of the Pomeranian Medical University, Szczecin, Poland to conduct the research (Resolution No. KB-0012/01/12 by the Bioethical Committee of Pomeranian Medical University, Szczecin, Poland from 13. February 2012).
Changes to lipid organization that result in cancer initiation and progression contribute to the understanding of carcinogenesis and identification of potential therapeutic targets. The activity of enzymes that participate in the synthesis and endogenous changes of fatty acids, probably created for a fast growing tumor, is higher in the tumor than in healthy tissues. The increased de novo synthesis of fatty acids is a feature of intensive tumor growth .
In conclusion, the results point to ATME as the microenvironment which is extremely active in lipid metabolism accompanying SCC of the oral cavity. This is reflected by high content of certain FAs mainly in ATME and decrease in frequency of some other FAs in tumor in comparison with ATME. ATME was the environment in which the greatest number of FAs showed differences in percentage content between G1+2 and G3 tumors and these differences were the largest. Primary role of tumor grade in these changes was revealed mainly in ATME although in all three environments, i.e. tumor, ATME and serum, tumor grade influenced the number and magnitude of associations between particular FAs.