|Table of Contents|

Activation of osteoclasts on dormant lung adenocarcinoma cells and its molecular mechanism

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

2023 13
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Activation of osteoclasts on dormant lung adenocarcinoma cells and its molecular mechanism
GUI Pengcheng12QIU Rong2WEI Lirong2TENG Xiaoyan2DU Yuzhen12
1.College of Fisheries and Life Science,Shanghai Ocean University,Shanghai 201306,China;2.Department of Laboratory Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 201306,China.
osteoclastsdormancylung adenocarcinoma cellsAMPK/mTOR signaling pathway
Objective:To investigate the activation effect of osteoclasts on dormant lung adenocarcinoma(LUAD) cells H1975 and its potential molecular mechanism.Methods:A dormant model of lung adenocarcinoma cells was established by serum deprivation,and the proliferation and apoptosis levels of dormant lung adenocarcinoma cells,as well as the protein expression of senescence and dormancy-related markers by β-galactosidase,were assayed.Human peripheral blood mononuclear cells were isolated and cultured,and the differentiation of human peripheral blood mononuclear cells into mature osteoclasts was induced by M-CSF and h-RANKL factors.The osteoclasts were identified by TARP staining,and the culture supernatants of osteoclasts were collected.The supernatants of osteoclasts were co-cultured with dormant lung adenocarcinoma cells,and the cell cycle and proliferation were assayed by flow cytometry,the cell migration ability was detected by Transwell,and the expression of dormancy-related and AMPK signaling pathway-related proteins was detected by Western blot.Results:In vitro serum deprivation induced dormancy in lung adenocarcinoma cell line H1975 with cell cycle arrest in G0-G1 phase,proliferation arrest and upregulation of dormancy-related markers Nanog,NR2F1,p27 and p21.In vitro human peripheral blood mononuclear cells induced differentiation of osteoclasts culture system was established.The culture supernatant of osteoclasts cells had the ability to promote dormant lung adenocarcinoma cell cycle recovery,cell proliferation and cell migration.Meanwhile,the down-regulation of dormancy-related protein expression was associated with AMPK dephosphorylation and mTOR phosphorylation of AMPK signaling pathway.Conclusion:Osteoclasts have a role in promoting the activation of dormant lung adenocarcinoma cells,and the molecular mechanism was related to AMPK signaling pathway.


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National Natural Science Foundation of China(No.81974315);国家自然科学基金(编号:81974315)
Last Update: 2023-05-31