Cancer‐associated fibroblast‐derived interleukin‐1β activates protumor C‐C motif chemokine ligand 22 signaling in head and neck cancer

Huang, Yu-Hsuan; Chang, Che Ying; Kuo, Yi Zih; Fang, Wei; Kao, Hung Ying; Tsai, Sen Tien; Wu, Li-Wha

doi:10.1111/cas.14135

Cited by 50 publications

(32 citation statements)

References 42 publications

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“…Previous studies reported that CCL22 could recruit FOXP3 (+) regulatory T-cells. Increased CCL22 mRNA levels are correlated with increased FoxP3 mRNA levels in oral cancer specimens [43]. In a B16F10 melanoma model, imiquimod (IQM) has been shown to reduce T-regs at the tumor site by the downregulation of CCL22 production [44].…”

Section: Discussionmentioning

confidence: 99%

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Higher CCL22+ Cell Infiltration is Associated with Poor Prognosis in Cervical Cancer Patients

Wang

Schmoeckel

Kost

et al. 2019

Cancers

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The chemokine CCL22 recruits regulatory T (T-reg) cells into tumor tissues and is expressed in many human tumors. However, the prognostic role of CCL22 in cervical cancer (CC) has not been determined. This study retrospectively analyzed the clinical significance of the expression of CCL22 and FOXP3 in 230 cervical cancer patients. Immunohistochemical staining analyses of CCL22 and FOXP3 were performed with a tissue microarray. Double immunofluorescence staining, cell coculture, and ELISA were used to determine CCL22 expressing cells and mechanisms. The higher number of infiltrating CCL22+ cells (CCL22 high ) group was associated with lymph node metastasis (p = 0.004), Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stages (p = 0.010), therapeutic strategies (p = 0.007), and survival status (p = 0.002). The number of infiltrating CCL22+ cells was positively correlated with that of infiltrating FOXP3+ cells (r = 0.210, p = 0.001). The CCL22 high group had a lower overall survival rate (OS), compared to the CCL22 low group (p = 0.001). However, no significant differences in progression free survival (PFS) were noted between the two groups. CCL22 high was an independent predictor of shorter OS (HR, 4.985; p = 0.0001). The OS of the combination group CCL22 high FOXP3 high was significantly lower than that of the combination group CCL22 low FOXP3 low regardless of the FIGO stage and disease subtype. CCL22 high FOXP3 high was an independent indictor of shorter OS (HR, 5.284; p = 0.009). The PFS of group CCL22 high FOXP3 high was significantly lower than that of group CCL22 low FOXP3 low in cervical adenocarcinoma, but CCL22 high FOXP3 high was not an independent indicator (HR, 3.018; p = 0.068). CCL22 was primarily expressed in M2-like macrophages in CC and induced by cervical cancer cells. The findings of our study indicate that cervical cancer patients with elevated CCL22+ infiltrating cells require more aggressive treatment. Moreover, the results provide a basis for subsequent, comprehensive studies to advance the design of immunotherapy for cervical cancer.

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Section: Discussionmentioning

confidence: 99%

“…Several studies have investigated the source of CCL22. For instance, Huang et al proved that CCL22 was overexpressed in head and neck cancer cells [43]. CCL22 was found in macrophages of tongue squamous cell carcinoma [46].…”

Section: Discussionmentioning

confidence: 99%

Higher CCL22+ Cell Infiltration is Associated with Poor Prognosis in Cervical Cancer Patients

Wang

Schmoeckel

Kost

et al. 2019

Cancers

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“…Moreover, IL-1β plays an important role in tumor microenvironment. IL-1β can increase the proliferation of dysplasia oral cells, stimulate oncogenic cytokines, and promote aggressiveness of OSCC [39,57]. Similar to the abovementioned genes, MMP2 was found to be overexpressed in HNSCC.…”

Section: Discussionmentioning

confidence: 76%

Combination of β2-AR Blocker and COX-2 Inhibitor Suppresses Development of Oral Squamous Cell Carcinoma

Zhang¹,

Ma²,

Liao³

et al. 2020

Preprint

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Background To study the effect of inhibiting progression of oral squamous cell carcinoma (OSCC) through blocking β2-adrenergic receptor (β2-AR) and inhibiting Cyclooxygenase-2 (COX-2). Methods Transwell invasion assay and wound-healing assay were used to investigate whether invasion and metastasis of OSCC cells (SCC9, Cal27 cell lines and primary OSCC cells) would be inhibited after treated by β2-AR blocker (ICI118,551), COX-2 inhibitor (Etodolac) or both. Real time quantitative polymerase chain reaction (RT-qPCR), Western blot and enzyme linked immunosorbent assay (ELISA) were used to detect expression change of genes related to invasion and metastasis in OSCC cells after drug treatment. In vivo, 6-8 weeks old female Balb/c nude mice were randomly divided into control group, ICI118,551 treatment group, etodolac treatment group and combined treatment group. Cal27 cells were used to establish OSCC xenograft models. The survival days, tumor sizes and lymph nodes metastasis were compared among these groups. Immunohistochemistry, Western blot and ELISA were carried out to detect expression change of invasion and metastasis relative genes. Results ICI118,551 or etodolac could inhibit invasion and metastasis of OSCC cells, and the inhibition of combined treatment was more significant. Moreover, RT-qPCR and Western blot showed that epidermal growth factor receptor (EGFR), transforming growth factor-β1 (TGF-β1), interleukin-1β (IL-1β), matrix metalloproteinase 2 (MMP2) were downregulated after treatment, especially in combined treatment group. In vivo, the combined treatment group could significantly prolong survival days and inhibit tumor size. Immunohistochemistry, Western blot and ELISA showed the expression of above-mentioned genes were also downregulated. Conclusions Invasion and metastasis of OSCC can be inhibited through blocking β2-AR and inhibiting COX-2, it can be a potential treatment of OSCC.

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“…In addition, the four overlapping target genes of miR-7977 (CCL22, STK4, HSPA1B, and ACTR2) in all three databases were reported to have a key role in cancer formation and metastasis. Studies have shown that these genes are involved in the growth, invasion, and metastasis of a variety of tumors, and that they play a key role in tumorrelated molecular mechanisms (30)(31)(32)(33). Furthermore, abnormal signaling pathways also play crucial roles in the development of cancer metastasis.…”

Section: Discussionmentioning

confidence: 99%

Identification of Cerebrospinal Fluid MicroRNAs Associated With Leptomeningeal Metastasis From Lung Adenocarcinoma

Pan

Yang

et al. 2020

Front. Oncol.

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Background: Leptomeningeal metastasis (LM) has frequently been observed in patients with lung adenocarcinoma. So far, its diagnosis and disease course monitoring are still extremely difficult. Moreover, there is no effective treatment regimen for LM due to a lack knowledge on the molecular mechanism of LM. This study aimed to identify LM-related cerebrospinal fluid (CSF) miRNAs, which have potential value for diagnosing and monitoring LM and exploring the molecular mechanism. Methods: CSF miRNAs were screened and verified by microarray analysis and quantitative real-time PCR (qRT-PCR) in LM patients with lung adenocarcinoma and non-LM controls, and the diagnostic performance of candidate miRNAs was evaluated. Then, candidate miRNAs in matched CSF samples from LM patients at diagnosis, after initial therapy, at relapse, and after salvage therapy, were analyzed to assess the relationship between CSF miRNAs and LM disease course. The effect of candidate miRNAs on proliferation, invasion, and migration of lung adenocarcinoma cell lines was assessed. The targeted genes of the candidate miRNA were predicted by TargetScan, miRDB, and miRTarbase online analysis tools. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the functional categories of predicted target genes. Results: CSF miR-7975, miR-7977, and miR-7641 were screened and verified to be statistically significantly up-regulated in LM patients compared to non-LM controls. The three miRNAs, when combined, exhibited optimal diagnostic performance. Longitudinal data of CSF miR-7975 and miR-7977 correlated well with clinical courses of LM. Overexpression of miR-7977 promoted proliferation, migration, and invasion of lung adenocarcinoma cells. Moreover, 385 targeted genes of miR-7977 were predicted and were involved in various pathways related to cancer metastasis. Conclusions: This study offers insights for future research of CSF miRNAs as robust tools for diagnosing and monitoring LM. It also reveals a novel pathway for exploration of underlying mechanisms of LM.

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Cancer‐associated fibroblast‐derived interleukin‐1β activates protumor C‐C motif chemokine ligand 22 signaling in head and neck cancer

Cited by 50 publications

References 42 publications

Higher CCL22+ Cell Infiltration is Associated with Poor Prognosis in Cervical Cancer Patients

Higher CCL22+ Cell Infiltration is Associated with Poor Prognosis in Cervical Cancer Patients

Combination of β2-AR Blocker and COX-2 Inhibitor Suppresses Development of Oral Squamous Cell Carcinoma

Identification of Cerebrospinal Fluid MicroRNAs Associated With Leptomeningeal Metastasis From Lung Adenocarcinoma

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