CCR3 blockage elicits polyploidization associated with the signatures of epithelial-mesenchymal transition in carcinoma cell lines

Kaibori, Yuichiro; Nagakubo, Daisuke

doi:10.1038/s41417-022-00532-8

Cited by 3 publications

(2 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, studies in other types of cancer have shown that CCR3 plays a major role in promoting tumor progression and is strongly associated with poor prognosis of patients, with its role in the TIME exhibited through the recruitment of TAMs to facilitate tumor progression (5,(28)(29)(30). In addition, it has been found that inhibition of CCR3 in cancer cell lines induces polyploid giant cell formation and b-catenin stabilization through the PI3K/Akt/GSK-3b signaling pathway, a process associated with EMT, as a result of CCR3 inhibition, transformed cells acquired enhanced mobility and proliferation (31). Non-polarized (M0) macrophages are derived from monocytes following colony-stimulating factor 1 (CSF-1) induction.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis and immune landscape of chemokines- and chemokine receptors-based signature in hepatocellular carcinoma

et al. 2023

View full text Add to dashboard Cite

BackgroundDespite encouraging results from immunotherapy combined with targeted therapy for hepatocellular carcinoma (HCC), the prognosis remains poor. Chemokines and their receptors are an essential component in the development of HCC, but their significance in HCC have not yet been fully elucidated. We aimed to establish chemokine-related prognostic signature and investigate the association between the genes and tumor immune microenvironment (TIME).Methods342 HCC patients have screened from the TCGA cohort. A prognostic signature was developed using least absolute shrinkage and selection operator regression and Cox proportional risk regression analysis. External validation was performed using the LIHC-JP cohort deployed from the ICGC database. Single-cell RNA sequencing (scRNA-seq) data from the GEO database. Two nomograms were developed to estimate the outcome of HCC patients. RT-qPCR was used to validate the differences in the expression of genes contained in the signature.ResultsThe prognostic signature containing two chemokines-(CCL14, CCL20) and one chemokine receptor-(CCR3) was successfully established. The HCC patients were stratified into high- and low-risk groups according to their median risk scores. We found that patients in the low-risk group had better outcomes than those in the high-risk group. The results of univariate and multivariate Cox regression analyses suggested that this prognostic signature could be considered an independent risk factor for the outcome of HCC patients. We discovered significant differences in the infiltration of various immune cell subtypes, tumor mutation burden, biological pathways, the expression of immune activation or suppression genes, and the sensitivity of different groups to chemotherapy agents and small molecule-targeted drugs in the high- and low-risk groups. Subsequently, single-cell analysis results showed that the higher expression of CCL20 was associated with HCC metastasis. The RT-qPCR results demonstrated remarkable discrepancies in the expression of CCL14, CCL20, and CCR3 between HCC and its paired adjacent non-tumor tissues.ConclusionIn this study, a novel prognostic biomarker explored in depth the association between the prognostic model and TIME was developed and verified. These results may be applied in the future to improve the efficacy of immunotherapy or targeted therapy for HCC.

show abstract

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis and immune landscape of chemokines- and chemokine receptors-based signature in hepatocellular carcinoma

et al. 2023

View full text Add to dashboard Cite

show abstract

“…RT-PCR was performed as previously described [ 29 ]. Briefly, SMGs obtained from WT and CCL28-deficient mice were lysed in TRIzol reagent (Thermo Fisher Scientific, Waltham, MA, USA), and cDNA was prepared by RT using the ReverTra Ace qPCR RT Master Mix (Toyobo, Osaka, Japan).…”

Section: Methodsmentioning

confidence: 99%

CCL28: A Promising Biomarker for Assessing Salivary Gland Functionality and Maintaining Healthy Oral Environments

Kaibori,

Tamoto,

Okuda

et al. 2024

Biology

Self Cite

View full text Add to dashboard Cite

The oral cavity serves as the primary path through which substances from the outside world enter our body. Therefore, it functions as a critical component of host defense. Saliva is essential for maintaining a stable oral environment by catching harmful agents, including pathogens, allergens, and chemicals, in the air or food. CCL28, highly expressed in mucosal tissues, such as the colon and salivary glands, is a chemokine that attracts CCR10/CCR3 expressing cells. However, the role of CCL28 in salivary gland formation remains unclear. In this study, we investigated the salivary gland structure in CCL28-deficient mice. Histological analysis showed decreased staining intensity of Alcian blue, which detects acidic mucous, reduced expression of MUC2, and higher infiltration of gram-positive bacteria in the salivary glands of CCL28-deficient mice. In addition, CCL28-deficient mice contained ectopically MUC2-expressed cells in the ducts and reduced the expression of cytokeratin 18, a marker for ductal cells, within the submandibular glands, resulting in decreased duct numbers. Additionally, the submandibular glands of CCL28-deficient mice showed reduced expression of several stem cell markers. These results suggest that CCL28 regulates saliva production via proper differentiation of salivary gland stem cells and could be a valuable biomarker of salivary gland function.

show abstract

Dormant cancer cells and polyploid giant cancer cells: The roots of cancer recurrence and metastasis

Jiao,

Yu,

Zheng

et al. 2024

Clinical & Translational Med

View full text Add to dashboard Cite

Tumour cell dormancy is critical for metastasis and resistance to chemoradiotherapy. Polyploid giant cancer cells (PGCCs) with giant or multiple nuclei and high DNA content have the properties of cancer stem cell and single PGCCs can individually generate tumours in immunodeficient mice. PGCCs represent a dormant form of cancer cells that survive harsh tumour conditions and contribute to tumour recurrence. Hypoxic mimics, chemotherapeutics, radiation and cytotoxic traditional Chinese medicines can induce PGCCs formation through endoreduplication and/or cell fusion. After incubation, dormant PGCCs can recover from the treatment and produce daughter cells with strong proliferative, migratory and invasive abilities via asymmetric cell division. Additionally, PGCCs can resist hypoxia or chemical stress and have a distinct protein signature that involves chromatin remodelling and cell cycle regulation. Dormant PGCCs form the cellular basis for therapeutic resistance, metastatic cascade and disease recurrence. This review summarises regulatory mechanisms governing dormant cancer cells entry and exit of dormancy, which may be used by PGCCs, and potential therapeutic strategies for targeting PGCCs.

show abstract

CCR3 blockage elicits polyploidization associated with the signatures of epithelial-mesenchymal transition in carcinoma cell lines

Cited by 3 publications

References 47 publications

Comprehensive analysis and immune landscape of chemokines- and chemokine receptors-based signature in hepatocellular carcinoma

Comprehensive analysis and immune landscape of chemokines- and chemokine receptors-based signature in hepatocellular carcinoma

CCL28: A Promising Biomarker for Assessing Salivary Gland Functionality and Maintaining Healthy Oral Environments

Dormant cancer cells and polyploid giant cancer cells: The roots of cancer recurrence and metastasis

Contact Info

Product

Resources

About