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Tumor-associated macrophages affect the biological behavior of lung adenocarcinoma A549 cells through the PI3K/AKT
Shiyang Yuan1, Yaling Dong1, Laishui Peng1
1Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Abstract:
Tumor associated macrophages (TAMs) are a major type of inflammatory cell in a tumor microenvironment. Previous evidence has suggested that TAMs promote tumorigenesis, growth, invasion and metastasis, thereby affecting tumor metabolism. The mechanisms through which they affect the invasion and metastasis of lung cancer cells remain unclear. The present study investigated the effects and molecular mechanisms of TAMs on the proliferation, invasion and migration of lung adenocarcinoma A549 cells. Human mononuclear leukemia THP-1 cells were induced into TAMs. The morphological changes that occurred during the induction of the THP-1 cells were examined with a light microscope. Successful TAM formation was confirmed via flow cytometry. Proliferation, invasion and migration of the lung adenocarcinoma A549 cells were detected by EDU proliferation, scratch wound and Transwell invasion and migration assays, respectively. The expression levels of key proteins involved in the PI3K/AKT signaling pathway were detected by western blot analysis. It was identified that treatment with interleukin (IL)-4, IL-13 and Phorbol-12-myristate-13-acetate successfully induced THP-1 to form TAMs. The indirect coculture model of TAMs was established by Transwell chamber detection, and the proliferation, invasion and migration ability of lung adenocarcinoma A549 cells were enhanced. Western blot analysis indicated that the expression levels of phosphorylated (p)-PI3K and p-AKT proteins were significantly upregulated in the TAMs coculture group compared with that of the blank control group. In summary, the present study demonstrated that TAMs may promote the proliferation, invasion and migration of lung adenocarcinoma A549 cells in vitro, perhaps through the activation of the PI3K/AKT signaling pathway.
Insights
Tumor associated macrophages (TAMs) promote lung adenocarcinoma cell growth, invasion, and migration. This occurs possibly via activating the PI3K/AKT signaling pathway, suggesting new therapeutic targets.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Tumor associated macrophages (TAMs) are key inflammatory cells within the tumor microenvironment.
- TAMs are implicated in promoting tumor growth, invasion, and metastasis.
- The specific mechanisms by which TAMs influence lung cancer cell invasion and metastasis are not fully understood.
Purpose of the Study:
- To investigate the effects of TAMs on the proliferation, invasion, and migration of lung adenocarcinoma A549 cells.
- To elucidate the molecular mechanisms underlying TAM-mediated promotion of lung cancer progression.
- To examine the role of the PI3K/AKT signaling pathway in TAM-promoted lung cancer cell behaviors.
Main Methods:
- Human mononuclear leukemia THP-1 cells were differentiated into TAMs using IL-4, IL-13, and PMA.
- TAM formation was confirmed using light microscopy and flow cytometry.
- Lung adenocarcinoma A549 cell proliferation, invasion, and migration were assessed using EDU, scratch wound, and Transwell assays, respectively.
- Protein expression of the PI3K/AKT pathway was analyzed via Western blot.
Main Results:
- THP-1 cells were successfully induced into TAMs.
- Co-culture with TAMs significantly enhanced the proliferation, invasion, and migration of A549 lung cancer cells.
- Western blot analysis revealed significant upregulation of phosphorylated PI3K (p-PI3K) and phosphorylated AKT (p-AKT) in A549 cells co-cultured with TAMs.
- These findings suggest TAMs activate the PI3K/AKT signaling pathway.
Conclusions:
- TAMs promote the proliferation, invasion, and migration of lung adenocarcinoma cells in vitro.
- The PI3K/AKT signaling pathway is likely involved in the pro-tumorigenic effects of TAMs.
- Targeting TAMs or the PI3K/AKT pathway may represent a therapeutic strategy for lung adenocarcinoma.
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