Neoplasia最新文献

{"title":"Acquired vulnerability against EGF receptor inhibition in gastric cancer promoted by class I histone deacetylase inhibitor entinostat","authors":"Tamara Zenz ,&nbsp;Robert Jenke ,&nbsp;Denys Oliinyk ,&nbsp;Sandra Noske ,&nbsp;René Thieme ,&nbsp;Tim Kahl ,&nbsp;Ines Gockel ,&nbsp;Florian Meier-Rosar ,&nbsp;Achim Aigner ,&nbsp;Thomas RH Büch","doi":"10.1016/j.neo.2024.101121","DOIUrl":"10.1016/j.neo.2024.101121","url":null,"abstract":"<div><h3>Introduction</h3><div>Histone deacetylase inhibitors (HDACi) have shown promising preclinical activity in gastric cancer cells; unfortunately, however, these could not be confirmed in clinical trials. This highlights the need for the identification of underlying reasons, which may also provide the basis for possible combination therapies. Here, we delineated the effects of HDACi on components of EGFR signalling in gastric cancer cells.</div></div><div><h3>Methods</h3><div>We investigated entinostat effects on EGFR and amphiregulin (AREG) expression in various cell line- and primary patient tumor-based <em>in vitro, ex vivo</em> and <em>in vivo</em> models, on the mRNA and protein level. Based on these results, a combined entinostat plus EGFR inhibitor erlotinib treatment <em>in vitro</em> and <em>in vivo</em> was studied.</div></div><div><h3>Results</h3><div>Proteomics analyses in gastric cancer cells treated with entinostat revealed a marked upregulation of EGFR in the majority of cell lines and an even more robust induction of the EGFR ligand AREG. This was confirmed in a panel of different cell lines <em>in vitro</em>, in tumor tissue-slice cultures <em>ex vivo</em> and in cell line- or patient-derived tumor xenografts in mice. Since previous studies in other tumor entities showed a downregulation of EGFR by HDACi, our findings thus indicate essential differences in the adaptive response of gastric carcinoma cells. Moreover, our results provided the basis for combined entinostat + EGFR inhibitor (erlotinib) treatment, and indeed we demonstrate synergistic effects in combination therapy studies.</div></div><div><h3>Conclusion</h3><div>Our findings establish the profound upregulation of the EGFR/AREG axis by entinostat as starting point for a rational combination therapy in gastric carcinoma.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"60 ","pages":"Article 101121"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic and proteomic profiling identifies feline fibrosarcoma as clinically amenable model for aggressive sarcoma subtypes","authors":"Mikiyo Weber ,&nbsp;Daniel Fuchs ,&nbsp;Amiskwia Pöschel ,&nbsp;Erin Beebe ,&nbsp;Zuzana Garajova ,&nbsp;Armin Jarosch ,&nbsp;Laura Kunz ,&nbsp;Witold Wolski ,&nbsp;Lennart Opitz ,&nbsp;Franco Guscetti ,&nbsp;Mirja C. Nolff ,&nbsp;Enni Markkanen","doi":"10.1016/j.neo.2024.101104","DOIUrl":"10.1016/j.neo.2024.101104","url":null,"abstract":"<div><div>Fibrosarcomas (FSA) are malignant mesenchymal tumors characterized by low chemo- and radiosensitivity. Development of novel treatment strategies for human adult FSA is hindered by the low incidence and the absence of suitable clinical models. Interestingly, aggressive FSA occur more frequently in domestic cats, hence potentially representing a clinically amenable model to assess novel therapies such as targeted imaging or theranostics. However, a lack of molecular characterization of FSA and adjacent normal tissue (NT) in both species hinders identification of tumor-specific targets and undermines the translational potential of feline FSA. Combining laser-capture microdissection, RNAsequencing and liquid chromatography-tandem mass spectrometry, we perform comprehensive profiling of 30 feline FSA and matched skeletal muscle, adipose and connective tissue. Clear inter-tissue differences allow identification of significantly upregulated and tumor-exclusive features that represent potential targets for diagnostic and therapeutic approaches. While feline FSA are characterized by hyperactive EIF2, TP53 and MYC signaling, immune-related and neuronal pathways emerge as modulators of tumor aggressiveness and immunosuppression. A high degree of molecular similarity with canine and adult FSA allows identification of tumor targets that are conserved across species. Significant enrichment in DNA repair pathways in feline FSA correlate with aggressive clinical behavior in human soft-tissue sarcoma. Finally, we leverage the molecular profiles to identify vulnerabilities, including sensitivity to ATR and PARP inhibition as potential treatment for feline FSA. In conclusion, this detailed landscape provides a rich resource to identify target candidates and therapeutic vulnerabilities within and across species and supports feline FSA as relevant models for the human disease.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"60 ","pages":"Article 101104"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11713505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Informatics strategies for early detection and risk mitigation in pancreatic cancer patients","authors":"Di Jin ,&nbsp;Najeeb Ullah Khan ,&nbsp;Wei Gu ,&nbsp;Huijun Lei ,&nbsp;Ajay Goel ,&nbsp;Tianhui Chen","doi":"10.1016/j.neo.2025.101129","DOIUrl":"10.1016/j.neo.2025.101129","url":null,"abstract":"<div><div>This review provides a comprehensive overview of the current landscape in pancreatic cancer (PC) screening, diagnosis, and early detection. This emphasizes the need for targeted screening in high-risk groups, particularly those with familial predispositions and genetic mutations, such as BRCA1, BRCA2, and PALB2. This review highlights the sporadic nature of most PC cases and significant risk factors, including smoking, alcohol consumption, obesity, and diabetes. Advanced imaging techniques, such as Endoscopic Ultrasound (EUS) and Contrast-Enhanced Harmonic Imaging (CEH-EUS), have been discussed for their superior sensitivity in early detection. This review also explores the potential of novel biomarkers, including those found in body fluids, such as serum, plasma, urine, and bile, as well as the emerging role of liquid biopsy technologies in analyzing circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and exosomes. AI-driven approaches, such as those employed in Project Felix and CancerSEEK, have been highlighted for their potential to enhance early detection through deep learning and biomarker discovery. This review underscores the importance of universal genetic testing and the integration of AI with traditional diagnostic methods to improve outcomes in high-risk individuals. Additionally, this review points to future directions in PC diagnostics, including next-generation imaging, molecular biomarkers, and personalized medicine, aiming to overcome current diagnostic challenges and improve survival rates. Ultimately, the review advocates the adoption of informatics and AI-driven strategies to enhance early detection, reduce morbidity, and save lives in the fight against pancreatic cancer.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"60 ","pages":"Article 101129"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The chemokine CX3CL1 promotes intraperitoneal tumour growth despite enhanced T-cell recruitment in ovarian cancer","authors":"Stefanie Seitz ,&nbsp;Tobias F. Dreyer ,&nbsp;Christoph Stange ,&nbsp;Katja Steiger ,&nbsp;Dirk Wohlleber ,&nbsp;Martina Anton ,&nbsp;Thuý An Pham ,&nbsp;Dominique Sauter-Peschke ,&nbsp;Ute Reuning ,&nbsp;Gabriele Multhoff ,&nbsp;Wilko Weichert ,&nbsp;Marion Kiechle ,&nbsp;Viktor Magdolen ,&nbsp;Holger Bronger","doi":"10.1016/j.neo.2025.101130","DOIUrl":"10.1016/j.neo.2025.101130","url":null,"abstract":"<div><div>T-cell recruiting chemokines are required for a successful immune intervention in ovarian cancer, and also for the efficacy of modern anticancer agents such as PARP inhibitors. The chemokine CX3CL1 recruits tumour-suppressive T-cells into solid tumours, but also mediates cell–cell adhesions, e.g. of tumour cells, through its membrane-bound form. So far, its role in ovarian cancer has only been rudimentarily addressed. We show that high CX3CL1 expression significantly correlates with worsened survival in human high-grade serous ovarian cancer (n=219). In preclinical ovarian cancer, CX3CL1 plays a dual role, as it enhances the adaptive anti-tumour response, but overall still promotes tumour growth, the latter as a feature of the intraperitoneal environment. Moreover, PARP inhibitors are able to increase CX3CL1 release from human ovarian cancer cells. Collectively, our study shows that CX3CL1 is a driver of intraperitoneal tumour growth in ovarian cancer, a feature that may compromise the anticancer effect of CX3CL1-inducing PARP inhibitors.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"60 ","pages":"Article 101130"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of TUBB3 as an immunotherapy target in lung cancer by genome wide in vivo CRISPR screening","authors":"Dan Zhao ,&nbsp;Ravindra Deshpande ,&nbsp;Kerui Wu ,&nbsp;Abhishek Tyagi ,&nbsp;Sambad Sharma ,&nbsp;Shih-Ying Wu ,&nbsp;Fei Xing ,&nbsp;Stacey O'Neill ,&nbsp;Jimmy Ruiz ,&nbsp;Feng Lyu ,&nbsp;Kounosuke Watabe","doi":"10.1016/j.neo.2024.101100","DOIUrl":"10.1016/j.neo.2024.101100","url":null,"abstract":"<div><div>Recent development of immune checkpoint inhibitors has revolutionized cancer immunotherapy. Although these drugs show dramatic effects on a subset of cancer patients, many other tumors are non-responsive and the pathological mechanism of the resistance is largely unknown. To identify genes underlying anti-PD-1 immunotherapy resistance using a systematic approach, we performed an <em>in vivo</em> genome wide CRISPR screening in lung cancer cells. We integrated our results with multi-omics clinical data and performed both <em>in vitro</em> and <em>in vivo</em> assays to evaluate the role of the top candidate in regulating cytotoxic T cell killing. We identified TUBB3 as a potential target to overcome the resistance and enhance the efficacy of anti-PD-1 immunotherapy. TUBB3 expression is upregulated in lung cancer patients, and its higher expression correlates with poorer patients’ survival. We found that TUBB3 expression was significantly elevated in the non-responders compared to responders in our patient cohort that received immunotherapies. Importantly, the results of our preclinical experiments showed that inhibition of TUBB3 with a small molecule inhibitor synergized with anti-PD-1 treatment and enhanced tumor cell killing by cytotoxic T cells. Consistently, anti-PD-1 resistant cells showed significantly higher expression of TUBB3; however, TUBB3 inhibition rendered the resistant cells more susceptible to T cell killing. Mechanistic studies revealed that blocking TUBB3 suppressed the expression of PD-L1 through the EMT-related SNAI1 gene. Our results provide a rationale for a novel combination therapy consisting of the TUBB3 inhibition and anti-PD-1 immunotherapy for lung cancer.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"60 ","pages":"Article 101100"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Tumorigenicity of IL-1α- and IL-1β-Deficient Fibrosarcoma Cells” [Neoplasia, Volume 10, Issue 6, June 2008, Pages 549–562]","authors":"Irina Nazarenko ,&nbsp;Rachid Marhaba ,&nbsp;Eli Reich ,&nbsp;Elena Voronov ,&nbsp;Mario Vitacolonna ,&nbsp;Dagmar Hildebrand ,&nbsp;Elena Elter ,&nbsp;Mohini Rajasagi ,&nbsp;Ron N. Apte ,&nbsp;Margot Zöller","doi":"10.1016/j.neo.2024.101087","DOIUrl":"10.1016/j.neo.2024.101087","url":null,"abstract":"","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"60 ","pages":"Article 101087"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RUNX2 enhances bladder cancer progression by promoting glutamine metabolism","authors":"Zhigang Huang ,&nbsp;Bin Liu ,&nbsp;Xiaoju Li ,&nbsp;Chenghua Jin ,&nbsp;Quansen Hu ,&nbsp;Zhiwei Zhao ,&nbsp;Yimin Sun ,&nbsp;Qian Wang","doi":"10.1016/j.neo.2024.101120","DOIUrl":"10.1016/j.neo.2024.101120","url":null,"abstract":"<div><div>Bladder cancer is a prevalent malignancy within the urinary system. Prior research has suggested that glutamine metabolism plays a crucial role in driving bladder cancer progression. However, the precise molecular mechanism governing glutamine metabolism in bladder cancer is still inadequately understood. The research revealed a significant correlation between high levels of RUNX2 and SLC7A6 and advanced clinical stage, as well as poor prognosis, in bladder cancer patients. Furthermore, manipulating the levels of RUNX2 through overexpression or silencing demonstrated a significant impact on glutamine and bladder cancer progression. Mechanically, RUNX2 regulates the transcription of SLC7A6, resulting in enhanced glutamine metabolism and promoting the progression of bladder cancer. Overall, this research affirms the crucial function of RUNX2 as a key transcription factor to promoting glutamine and cancer development through modulation of SLC7A6. Targeting RUNX2 could represent a promising therapeutic approach for addressing aberrant glutamine metabolism in bladder cancer.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"60 ","pages":"Article 101120"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical utility and predictive value of cerebrospinal fluid cell-free DNA profiling in non-small cell lung cancer patients with leptomeningeal metastasis","authors":"Sheng-Kai Liang ,&nbsp;Wei-Yu Liao ,&nbsp;Jin-Yuan Shih ,&nbsp;Chia-Lin Hsu ,&nbsp;Ching-Yao Yang ,&nbsp;Shang-Gin Wu ,&nbsp;Yen-Ting Lin ,&nbsp;Yueh-Feng Wen ,&nbsp;Lun-Che Chen ,&nbsp;Yen-Fu Chen ,&nbsp;Ya-Fang Chen ,&nbsp;Yen-Heng Lin ,&nbsp;Chong-Jen Yu","doi":"10.1016/j.neo.2024.101113","DOIUrl":"10.1016/j.neo.2024.101113","url":null,"abstract":"<div><div>Leptomeningeal metastasis (LM) is a challenging complication of non-small cell lung cancer (NSCLC). Cerebrospinal fluid (CSF) cell-free DNA (cfDNA) analysis using next-generation sequencing (NGS) offers insights into resistance mechanisms and potential treatment strategies. We conducted a study from February 2022 to April 2023 involving patients from five hospitals in Taiwan who had recurrent or advanced NSCLC with LM. These patients underwent CSF cfDNA analysis using a 118-gene targeted panel for NGS, with comprehensive clinical data collected. Among 25 enrolled patients, 22 (88.0 %) had <em>EGFR</em> mutations, while three (12.0 %) had <em>EML4-ALK</em> fusion, <em>KIF5B-RET</em> fusion, and <em>ERBB2</em> A775_G776insSVMA. CSF cfDNA sequencing of 27 samples (from 25 patients) all confirmed their original driver mutations. Of total cohort, 18 patients (72.0 %) underwent intrathecal pemetrexed (ITP), with a median survival time of 7.4 months (95.0 % confidence interval, 3.3–11.6) from the initiation of ITP to death. Among them, ten individuals (55.6 %) survived beyond 6 months. Notably, <em>MET</em> copy number gain (CNG) correlated significantly with survival time exceeding 6 months after ITP (<em>p</em> = 0.007). The coexistence of <em>EGFR</em> T790M and EGFR-independent resistance alterations was associated with shorter survival times after ITP, with a median survival time of 1.9 months compared to 9.9 months for those without <em>EGFR</em> T790M (<em>p</em> = 0.010). Our results highlight CSF cfDNA NGS's potential in LM resistance understanding and ITP efficacy prediction. <em>MET</em> CNG positively impacts survival for ITP recipients, whereas the coexistence <em>of EGFR</em> T790M and EGFR-independent resistance mechanisms leads to poor outcomes.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"60 ","pages":"Article 101113"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USP20 mediates malignant phenotypic changes in bladder cancer through direct interactions with YAP1","authors":"Wensun Chen ,&nbsp;Siqi Wu ,&nbsp;Yifan Chen ,&nbsp;Weijian Li ,&nbsp;Yiqing Cao ,&nbsp;Yingchun Liang ,&nbsp;Xiyu Dai ,&nbsp;Xinan Chen ,&nbsp;Yilin Chen ,&nbsp;Tian Chen ,&nbsp;Shenghua Liu ,&nbsp;Chen Yang ,&nbsp;Haowen Jiang","doi":"10.1016/j.neo.2024.101102","DOIUrl":"10.1016/j.neo.2024.101102","url":null,"abstract":"<div><div>Yes-associated protein 1 (YAP1) has attracted attention for its potential in the treatment of various types of malignancies. The Hippo-YAP1 axis is inhibited in bladder cancer (BC), which is a major driver of BC progression and oncogenesis. Hippo pathway activity is controlled by the phosphorylation cascade in the MST1/2-LATS1/2-YAP1 axis, in addition to other modifications such as ubiquitination of the Hippo pathway proteins through the co-regulation of E3 ligases and deubiquitinases. In this study, we identified USP20 as a Hippo/YAP1 pathway-related deubiquitinase using combined siRNA screening and a deubiquitinase overexpression assay. Further analysis revealed that USP20 directly regulated the expression of YAP1 and its downstream target genes connective tissue growth factor and cysteine-rich angiogenic inducer 61. A tissue microarray assay confirmed that USP20 expression was elevated in tumor tissues and correlated with YAP1 expression. Analysis of the underlying mechanisms revealed that USP20 directly interacted with the YAP1 protein and promoted its stability through inhibition of K48-linked poly-ubiquitination. Our findings revealed that USP20 serves as a deubiquitinase and regulates the Hippo-YAP1 pathway in BC.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"60 ","pages":"Article 101102"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-associated macrophages promote bladder cancer metastasis through the CCL20-CCR6 axis","authors":"Ryunosuke Nakagawa ,&nbsp;Kouji Izumi ,&nbsp;Kaoru Hiratsuka ,&nbsp;Takahiro Inaba ,&nbsp;Yoshiki Koketsu ,&nbsp;Ren Toriumi ,&nbsp;Shuhei Aoyama ,&nbsp;Taiki Kamijima ,&nbsp;Hiroshi Kano ,&nbsp;Tomoyuki Makino ,&nbsp;Renato Naito ,&nbsp;Suguru Kadomoto ,&nbsp;Hiroaki Iwamoto ,&nbsp;Hiroshi Yaegashi ,&nbsp;Shohei Kawaguchi ,&nbsp;Takahiro Nohara ,&nbsp;Kazuyoshi Shigehara ,&nbsp;Hiroki Nakata ,&nbsp;Wen-Jye Lin ,&nbsp;Atsushi Mizokami","doi":"10.1016/j.neo.2024.101103","DOIUrl":"10.1016/j.neo.2024.101103","url":null,"abstract":"<div><div>We investigated the mechanisms of interaction between bladder cancer (BC) cells and tumor-associated macrophages (TAMs). Coculturing BC cell lines (UMUC3 and T24) with macrophage-like cells differentiated from THP-1 into M2-like TAMs revealed a decrease in Cluster of Differentiation (CD) 68 expression and an increase in CD206 expression. This differentiation enhanced BC cell migration and invasion. Additionally, M2-like TAMs significantly increased the secretion of C–C motif chemokine ligand (CCL) 20, which promotes BC cell migration and invasion via the MEK/ERK signaling pathway through its paracrine effects. Coculturing with TAMs also elevated the expression of CC chemokine receptor (CCR) 6 in BC cells, indicating increased sensitivity to CCL20. Immunohistochemistry analysis of human BC tissues showed a significant correlation between CCR6 expression levels and BC prognosis. Inhibition of CCR6 reduced BC cell metastasis both in vitro and in vivo. Additionally, CXCL1 secretion from BC cells was found to contribute to the M2-like polarization of macrophages and to enhance BC cell migration and invasion through autocrine and indirect effects. In summary, CCL20 and CXCL1 play crucial roles in the interaction between BC cells and TAMs.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"60 ","pages":"Article 101103"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}