Tumor‑associated macrophages affect the biological behavior of lung adenocarcinoma A549 cells through the PI3K/AKT signaling pathway

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.

Tumor-Associated Macrophages in Human Breast, Colorectal, Lung, Ovarian and Prostate Cancers

“…Numerous studies confirmed that in lung cancer TAMs contribute to tumor progression and metastasis through the production of variety of chemokines and growth factors (156,(161)(162)(163). In vitro lung carcinoma cells (human NSCLC A549 cells) induce polarization of THP-1 cells to CD206+ M2 phenotype (156).…”

Matrix stiffness‐mediated effects on macrophages polarization and their LOXL2 expression

“…M2 macrophages are tumor-supportive cells and are characterized by high levels of IL-10, CC-chemokine ligand 18 (CCL18), CC-chemokine ligand 22 (CCL22), and matrix metalloproteinase 9 (MMP9) [24,25]. And M2 macrophages bear a striking resemblance to TAMs [26], which is an important component of tumor immune microenvironment [27,28]. In addition to chemical inducers, matrix stiffness also participates in inducing THP-1 cell polarization [29].…”

Curcumin-Loaded Solid Lipid Nanoparticles Bypass P-Glycoprotein Mediated Doxorubicin Resistance in Triple Negative Breast Cancer Cells

“…In co-culture assays, 1 × 10 5 human monocytic THP-1 cells (ATCC ® ), seeded in RPMI-1640 medium containing 10% FBS, were stimulated with 500 nM phorbol-12 myristate 13-acetate (PMA) for 24 h in order to favor their differentiation into macrophages [25]. Floating THP-1 cells were removed by washing the dishes twice with PBS; attached cells-i.e., macrophage-differentiated cells-were rinsed with fresh medium.…”