Sympathetic nerve infiltration promotes stomach adenocarcinoma progression via norepinephrine/β2-adrenoceptor/YKL-40 signaling pathway.

Autor:	Qi YH; Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, And the Department of Physiology, Shanxi Medical University, Taiyuan, China.; Department of Anesthesiology, Shanxi Provincial Peoples Hospital, Taiyuan, China., Yang LZ; Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, And the Department of Physiology, Shanxi Medical University, Taiyuan, China., Zhou L; Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, And the Department of Physiology, Shanxi Medical University, Taiyuan, China., Gao LJ; Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, And the Department of Physiology, Shanxi Medical University, Taiyuan, China., Hou JY; Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, And the Department of Physiology, Shanxi Medical University, Taiyuan, China., Yan Z; Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, And the Department of Physiology, Shanxi Medical University, Taiyuan, China., Bi XG; Department of Anesthesiology, Shanxi Provincial Peoples Hospital, Taiyuan, China., Yan CP; Center of Translational Medicine, Shanxi Medical University, Taiyuan, China., Wang DP; Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, And the Department of Physiology, Shanxi Medical University, Taiyuan, China., Cao JM; Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, And the Department of Physiology, Shanxi Medical University, Taiyuan, China.
Jazyk:	angličtina
Zdroj:	Heliyon [Heliyon] 2022 Dec 21; Vol. 8 (12), pp. e12468. Date of Electronic Publication: 2022 Dec 21 (Print Publication: 2022).
DOI:	10.1016/j.heliyon.2022.e12468
Abstrakt:	Objective: This study aimed to address the status, role, and mechanism of sympathetic nerve infiltration in the progression of stomach adenocarcinoma (STAD). Methods: Sympathetic nerve and its neurotransmitter NE, β-ARs, and associated signaling molecules in the STAD tissues and the adjacent tissues from 46 STAD patients were examined using immunostaining, HPLC, and western blotting. The effects and mechanisms of β2-AR activation on the proliferation, migration and invasion of AGS and SGC-7901 gastric cancer (GC) cell lines were examined using CCK-8, transwell, and western blotting assays. Correlations between genes and STAD survival were analyzed using bioinformatics. Results: Striking sympathetic nerve infiltration, elevations of NGF, TrkA, GAP43, TH, S100, NE, β2-AR, YKL-40, syndecan-1, MMP9, CD206, and CD31 were observed in the STAD tissues compared to the adjacent tissues. Activation of β2-AR in the two GC cell lines significantly amplified the expressions of NGF, YKL-40, MMP9, syndecan-1, p-STAT3 and p-ERK, and increased GC cell proliferation, migration and invasion. Bioinformatic analyses revealed positive correlations of NGF, β2-AR, syndecan-1, and macrophage infiltration, respectively, with low survival of STAD, of β2-AR respectively with STAT3, ERK1/2 (MAPK1/3), YKL-40, MMP9, and syndecan-1, and of YKL-40 with MMP9. Conclusion: Sympathetic nerves significantly infiltrated into human STAD tissues as a result of high NGF and TrkA expressions; elevated NE led to overactivation of β2-AR-STAT3/ERK-YKL-40 signaling pathway, and finally caused cancer cell growth and invasion, M2 macrophage infiltration, angiogenesis, matrix degradation and STAD metastasis and progression. Competing Interests: The authors declare no competing interests. Additional informationSupplementary content related to this article has been published online at https://doi.org/10.1016/j.heliyon.2022.e12468. (© 2022 The Author(s).)
Databáze:	MEDLINE
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