CC-Chemokine Ligand 18 Induces Epithelial to Mesenchymal Transition in Lung Cancer A549 Cells and Elevates the Invasive Potential

Ploenes, Till; Scholtes, B; Krause, Alexander; Burger, Meike; Passlick, Bernward; Müller–Quernheim, Joachim; Zissel, Gernot

doi:10.1371/journal.pone.0053068

Cited by 47 publications

(36 citation statements)

References 30 publications

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“…2). This is in line with Ploenes et al who reported about an enhanced chemotaxis in lung cancer cell lines with an increased chemoresistance (20).…”

Section: Discussionsupporting

confidence: 92%

“…Integrin β1 expression was upregulated in all gemcitabine-resistant sublines compared to parental cells. Integrin β4 expression was enhanced in TCC-SUP r GEMCI 20 and diminished in T24 r GEMCI 20 and in 5637 r GEMCI 20 . Comparing cisplatin-resistant cell lines, Integrin α3 expression was upregulated in 3 of 4 sublines (cisplatin-resistant sublines of T24, 5637, and TCC-SUP) and downregulated in HT1376 r CDDP…”

Section: Influence Of Acquired Chemoresistance On Chemotaxismentioning

confidence: 92%

“…, and TCC-SUP r GEMCI 20 . All cell lines were grown in Iscove's modified Dulbecco's medium supplemented with 10% fetal calf serum (FCS; Gibco, Karlsruhe, Germany), 100 IU/ml penicillin, and 100 µg/ml streptomycin at 37˚C.…”

Section: Drugsmentioning

confidence: 99%

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Blocking integrin β1 decreases adhesion in chemoresistant urothelial cancer cell lines

et al. 2017

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Abstract. Treatment failure in metastatic bladder cancer is commonly caused by acquisition of resistance to chemotherapy in association with tumor progression. Since alterations of integrins can influence the adhesive and invasive behaviors of urothelial bladder cancer cell lines, the present study aimed to evaluate the role of integrins in bladder cancer cells with acquired resistance to standard first-line chemotherapy with gemcitabine, and cisplatin. Therefore, four gemcitabineand four cisplatin-resistant sublines out of a panel of four parental urothelial bladder cancer cell lines (TCC-SUP, HT1376, T24, and 5637) were used. Expression of integrin subunits α3, α5, α6, β1, β3, and β4 was detected using flow cytometry. Adhesion and chemotaxis were analyzed. For functional assays, integrin β1 was attenuated with a blocking antibody. In untreated cells, chemotaxis was upregulated in 3/4 gemcitabine-resistant sublines. In cisplatin-resistant cells, chemotaxis was enhanced in 2/4 cell lines. Acquired chemoresistance induced the upregulation of integrin β1 in all four tested gemcitabine-resistant sublines, as well as an upregulation in 3/4 cisplatin-resistant sublines compared with parental cell lines. Following the inhibition of integrin β1, adhesion to extracellular matrix components was downregulated in 3/4 gemcitabine-resistant sublines and in all four tested cisplatin-resistant sublines. Since integrin β1 is frequently upregulated in chemoresistant urothelial cancer cell lines and inhibition of integrin β1 may influence adhesion, further studies are warranted to evaluate integrin β1 as a potential therapeutic target for bladder cancer in vivo.

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“…2). This is in line with Ploenes et al who reported about an enhanced chemotaxis in lung cancer cell lines with an increased chemoresistance (20).…”

Section: Discussionsupporting

confidence: 92%

Section: Influence Of Acquired Chemoresistance On Chemotaxismentioning

confidence: 92%

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Blocking integrin β1 decreases adhesion in chemoresistant urothelial cancer cell lines

et al. 2017

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“…In the tumor microenvironment, CCL18 promotes epithelial to mesenchymal transition in different types of solid tumors, including NSCLC (13)(14)(15). In a recently conducted study by Shi and colleagues, it was shown that CCL18 modulates NSCLC cell invasion and migration via the nitrite reductase 1-engulfment and cell motility 1/dedicator of cytokinesis 180 (NIR1-ELMO1/DOC180) pathway and thus promotes tumor metastasis (22).…”

Section: Discussionmentioning

confidence: 99%

“…CCL18 is responsible for the recruitment of naive T-cells and dendritic cells, and is capable of inducing regulatory T-cells. In the tumor microenvironment, it has been demonstrated to promote tumor spread and is believed to be one of the factors involved in the immune escape of tumor cells (13)(14)(15)(16)(17). …”

mentioning

confidence: 99%

Local Concentrations of CC-Chemokine-Ligand 18 Correlate with Tumor Size in Non-small Cell Lung Cancer and Are Elevated in Lymph Node-positive Disease

Schmid¹,

Le²,

Haager³

et al. 2016

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Lung cancer is the leading cause of cancer-related death and is usually diagnosed at an advanced stage, where lymph node/distant metastases are present. Only in about one-third of patients with non-small cell lung cancer (NSCLC) the disease is diagnosed as localized, for which a complete resection is the treatment of choice and a cure is possible. Hence, in most cases systemic therapy is required, either as part of a multimodal treatment or as sole therapeutic option. Despite advances in individualized approaches and modern chemotherapeutic regimens, the course of the disease remains unfavorable (1-3).It is widely acknowledged that the tumor microenvironment plays a critical role in tumor growth and spread, and in recent years, multiple therapeutic approaches have been developed based on this knowledge (4). In contrast to agents focusing on molecular targets such as the epidermal growth factor receptor (EGFR), and anaplastic lymphoma kinase (ALK), whose activity is confined to tumors with specific genetic alterations, immunotherapy is effective in various histological subtypes (5-8).Tumor microenvironment consists of tumor cells, the leukocyte infiltrate and the tumor associated immunologic microenvironment. One of the key players, the tumor associated macrophages (TAMs) can make up a large fraction of the tumor mass (9). Depending on the tumor microenvironment, macrophages can be polarized into different functional states, of which the two extremes are known as the M1 and M2 phenotypes. M1 macrophages have been shown to carry out pro-inflammatory, cytotoxic and thus mostly anti-neoplastic effects, whilst the M2 phenotype is responsible for tissue remodeling and repair and is believed to be involved in the subversion of adaptive immunity and thus the immunological interactions that promote tumor growth and progression. TAMs in the tumor microenvironment are mostly found to have the M2 phenotype (10). TAMs secrete a specific pattern of cytokines and chemokines and are one of the main producers of CC-chemokine ligand 18 (CCL18) in this context (11,12). CCL18 is responsible for the recruitment of naive T-cells and dendritic cells, and is capable of inducing regulatory T-cells. In the tumor microenvironment, it has been demonstrated to promote tumor spread and is believed to be one of the factors involved in the immune escape of tumor cells (13)(14)(15)(16)(17). 4667

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Global analysis of lysine acetylome reveals the potential role of CCL18 in non‐small cell lung cancer

et al. 2021

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C-C motif chemokine 18 (CCL18) belongs to the chemokine CC family and is predominantly secreted by M2-tumor-associated macrophages. It has been reported to be associated with various diseases and malignancies. Previous studies showed that CCL18 promotes metastasis by activating downstream kinases. However, it remains unknown whether CCL18 regulates post-translational modifications, other than phosphorylation, during tumorigenesis. Here, we demonstrate that CCL18 is up-regulated in non-small cell lung cancer (NSCLC) and is involved in regulating the lysine acetylome in A549 cells. Using the combination of SILAC labeling and high-efficiency acetylation enrichment methods, we identified 1372 lysine acetylation (Kac) sites on 796 proteins in CCL18-treated A549 cells. Among the identified Kac sites, 147 from 126 proteins were down-regulated and seven from five proteins were up-regulated with fold changes more than two and the p-value less than 0.05. Bioinformatics analysis further showed that the proteins with down-regulated acetylation play critical roles in glycolysis, oxidative phosphorylation, tricarboxylic acid cycle, and pentose phosphate pathway in A549 cells. These results suggest that CCL18 may be involved in the development of NSCLC by regulating acetylation of the proteins in many fundamental cellular processes, especially the metabolic reprogramming of tumor cells.

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CC-Chemokine Ligand 18 Induces Epithelial to Mesenchymal Transition in Lung Cancer A549 Cells and Elevates the Invasive Potential

Cited by 47 publications

References 30 publications

Blocking integrin β1 decreases adhesion in chemoresistant urothelial cancer cell lines

Blocking integrin β1 decreases adhesion in chemoresistant urothelial cancer cell lines

Local Concentrations of CC-Chemokine-Ligand 18 Correlate with Tumor Size in Non-small Cell Lung Cancer and Are Elevated in Lymph Node-positive Disease

Global analysis of lysine acetylome reveals the potential role of CCL18 in non‐small cell lung cancer

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