Cellular Oncology最新文献

{"title":"ZNF468-mediated epigenetic upregulation of VEGF-C facilitates lymphangiogenesis and lymphatic metastasis in ESCC via PI3K/Akt and ERK1/2 signaling pathways.","authors":"Jinrong Zhu, Xiangyu Qiu, Xin Jin, Xiaoya Nie, Shengming Ou, Geyan Wu, Jianfei Shen, Rongxin Zhang","doi":"10.1007/s13402-024-00976-0","DOIUrl":"10.1007/s13402-024-00976-0","url":null,"abstract":"<p><strong>Purpose: </strong>Dysfunctional lymphangiogenesis is pivotal for various pathological processes including tumor lymph node metastasis which is a crucial cause of therapeutic failure for ESCC. In this study, we aim to elucidate the molecular mechanisms and clinical relevance of Zinc-finger protein ZNF468 in lymphangiogenesis and lymphatic metastasis in ESCC.</p><p><strong>Methods: </strong>Immunohistochemistry, Western blot, Kaplan-Meier plotter analysis and Gene Set Enrichment Analysis were preformed to detect the association of ZNF468 with lymphangiogenesis and poor prognosis in ESCC patients. Foot-pads lymph node metastasis model, tube formation assay, 3D-culture assay and invasion assay were preformed to verify the effect of ZNF468 on lymphangiogenesis and lymph node metastasis. CUT&Tag analysis, immunoprecipitation and mass spectrometry analysis and ChIP-PCR assay were preformed to study the molecular mechanisms of ZNF468 in lymphangiogenesis.</p><p><strong>Results: </strong>We found that ectopic expression of ZNF468 was correlated with higher microlymphatic vessel density in ESCC tissues, leading to poorer prognosis of ESCC patients. ZNF468 enhanced the capacity of lymphangiogenesis and promoted lymphatic metastasis in ESCC both in vitro and in vivo. However, silencing ZNF468 reversed these phenotypes in ESCC. Mechanically, we demonstrated that ZNF468 recruits the histone modification factors (PRMT1/HAT1) to increase the levels of H4R2me2a and H3K9ac, which then leads to the recruitment of the transcription initiation complex on the VEGF-C promoter, ultimately promoting the upregulation of VEGF-C transcription. Strikingly, the promoting effect of lymphatic metastasis induced by ZNF468 in ESCC was abrogated by targeting PRMT1 using Arginine methyltransferase inhibitor-1 or silencing VEGF-C. Furthermore, we found that the activation of PI3K/AKT and ERK1/2 signaling is required for ZNF468-medicated lymphatic metastasis in ESCC. Importantly, the clinical relevance between ZNF468 and VEGF-C were confirmed not only in ESCC samples and but also in multiple cancer types.</p><p><strong>Conclusion: </strong>Our results identified a precise mechanism underlying ZNF468-induced epigenetic upregulation of VEGF-C in facilitating lymphangiogenesis and lymph node metastasis of ESCC, which might provide a novel prognostic biomarker and potential therapeutic for ESCC patients.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":"1927-1942"},"PeriodicalIF":6.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A dual-targeting approach with anti-IL10R CAR-T cells engineered to release anti-CD33 bispecific antibody in enhancing killing effect on acute myeloid leukemia cells.","authors":"Zhifeng Yan, Runxia Gu, Haotian Ma, Nianci Chen, Ting Zhang, Yingxi Xu, Shaowei Qiu, Haiyan Xing, Kejing Tang, Zheng Tian, Qing Rao, Min Wang, Jianxiang Wang","doi":"10.1007/s13402-024-00971-5","DOIUrl":"10.1007/s13402-024-00971-5","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapies, including chimeric antigen receptor (CAR) T cells and bispecific antibodies (BsAbs), encounter several challenges in the management of acute myeloid leukemia (AML), including limited persistence of these treatments, antigen loss and resistance of leukemia stem cells (LSCs) to therapy.</p><p><strong>Methods: </strong>Here, we proposed a novel dual-targeting approach utilizing engineered anti-IL10R CAR-T cells to secrete bispecific antibodies targeting CD33. This innovative strategy, rooted in our previous research which established a connection between IL-10 and the stemness of AML cells, designed to improve targeting efficiency and eradicate both LSCs and AML blasts.</p><p><strong>Results: </strong>We first demonstrated the superior efficacy of this synergistic approach in eliminating AML cell lines and primary cells expressing different levels of the target antigens, even in cases of low CD33 or IL10R expression. Furthermore, the IL10R CAR-T cells that secret anti-CD33 bsAbs (CAR.BsAb-T), exhibited an enhanced activation and induction of cytotoxicity not only in IL10R CAR-T cells but also in bystander T cells, thereby more effectively targeting CD33-positive tumor cells. Our in vivo experiments provided additional evidence that CAR.BsAb-T cells could efficiently redirect T cells, reduce tumor burden, and demonstrate no significant toxicity. Additionally, delivering bsAbs locally to the tumor sites through this strategy helps mitigate the pharmacokinetic challenges typically associated with the rapid clearance of prototypical bsAbs.</p><p><strong>Conclusions: </strong>Overall, the engineering of a single-vector targeting IL10R CAR, which subsequently secretes CD33-targeted bsAb, addresses the issue of immune escape due to the heterogeneous expression of IL10R and CD33, and represents a promising progress in AML therapy aimed at improving treatment outcomes.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":"1879-1895"},"PeriodicalIF":6.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing the spatial immune landscape of CD103⁺CD8⁺ tissue-resident memory T cells in non-small cell lung cancer by neoadjuvant chemotherapy.","authors":"Guanqun Yang, Mengyu Hu, Siqi Cai, Chaozhuo Li, Liying Yang, Miaoqing Zhao, Hongbiao Jing, Ligang Xing, Xiaorong Sun","doi":"10.1007/s13402-024-00980-4","DOIUrl":"10.1007/s13402-024-00980-4","url":null,"abstract":"<p><strong>Background: </strong>Neoadjuvant chemotherapy (NAC) combined with immunotherapy is increasingly used in non-small cell lung cancer (NSCLC). Tissue-resident memory T (T_RM) cells are the primary subset responding to anti-cancer immunity. However, the immunomodulatory effects of NAC on T_RM cells remain unknown.</p><p><strong>Methods: </strong>We established two NSCLC cohorts including patients undergoing upfront surgery (US) and NAC followed by surgery. Beyond the unpaired comparison between the US cohort (n = 122) and NAC cohort (n = 141) with resection samples, 58 matched pre-NAC biopsy samples were available for paired comparisons. Using multiplex immunofluorescence, we characterized T_RM cells (CD103⁺CD8⁺) and four heterogeneous T_RM subsets, including naive T_RM1 (PD-1^-Tim-3^-), pre-exhausted T_RM2 (PD-1⁺Tim-3^-), T_RM3 (PD-1^-Tim-3⁺), and terminally exhausted T_RM4 (PD-1⁺Tim-3⁺). Cell density, cytotoxicity, and two spatial features were defined to evaluate the effect of NAC on T_RM subsets.</p><p><strong>Results: </strong>The cell densities, infiltration scores, and cancer-cell proximity scores of T_RM cells, especially T_RM1&2 subsets, were significantly increased after NAC and associated with better prognosis of patients. In Contrast, no significant change was observed in the T_RM4 subset, which was associated with poor prognosis. Besides, the cytotoxicity of T_RM subsets was unaltered after NAC. Compared with patients without major pathologic response (MPRs), patients with MPR had higher densities of T_RM1&2 subsets and higher cancer-cell proximity scores of T_RM2&3 subsets. Furthermore, increased density of CD31 + cancer microvessels was positively associated with both T_RM and T_non-RM cells after NAC.</p><p><strong>Conclusions: </strong>NAC may remodel the cell density and spatial distribution of T_RM subsets, which is associated with favorable therapeutic effect and prognosis in patients with NSCLC.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":"1957-1971"},"PeriodicalIF":6.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA transcriptomic analyses of tumor microenvironment of ovarian metastasis in gastric cancer.","authors":"Guoyu Chen, Mingda Zhang, Xiaolin Lin, Qiqi Shi, Chenxin Xu, Bowen Sun, Xiuying Xiao, Haizhong Feng","doi":"10.1007/s13402-024-00974-2","DOIUrl":"10.1007/s13402-024-00974-2","url":null,"abstract":"<p><strong>Purpose: </strong>Ovarian metastasis of gastric cancer (GC), commonly referred to as Krukenberg tumors, leads to a poor prognosis. However, the cause of metastasis remains unknown. Here, we present an integrated single-cell RNA sequencing (scRNA-Seq) analysis of the immunological microenvironment of two paired clinical specimens with ovarian metastasis of GC.</p><p><strong>Methods: </strong>scRNA-Seq was performed to determine the immunological microenvironment in ovarian metastasis of gastric cancer. CellChat was employed to analyze cell-cell communications across different cell types. Functional enrichment analysis was done by enrichKEGG in clusterProfiler. GEPIA2 was used to assess the influence of certain genes and gene signatures on prognosis.</p><p><strong>Results: </strong>The ovarian metastasis tissues exhibit a heterogenous immunological microenvironment compared to the primary tumors. Exhaustion of T and B cells is observed in the ovarian metastasis tissues. Compared to the paired adjacent non-tumoral and primary tumors, the ratio of endothelial cells and fibroblasts is high in the ovarian metastasis tissues. Compared to primary ovarian cancers, we identify a specific group of tumor-associated fibroblasts with MFAP4 and CAPNS1 expression in the ovarian metastatic tissues of GC. We further define metastasis-related-endothelial and metastasis-related-fibroblast signatures and indicate that patients with these high signature scores have a poor prognosis. In addition, the ovarian metastasis tissue has a lower level of intercellular communications compared to the primary tumor.</p><p><strong>Conclusion: </strong>Our findings reveal the immunological microenvironment of ovarian metastasis of gastric cancer and will promote the discovery of new therapeutic strategies for ovarian metastasis in gastric cancer.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":"1911-1925"},"PeriodicalIF":6.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Panoramic tumor microenvironment in pancreatic ductal adenocarcinoma.","authors":"Xiaoying Li, Wanting Hou, Chaoxin Xiao, Heqi Yang, Chengjian Zhao, Dan Cao","doi":"10.1007/s13402-024-00970-6","DOIUrl":"10.1007/s13402-024-00970-6","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is notorious for its resistance to various treatment modalities. The genetic heterogeneity of PDAC, coupled with the presence of a desmoplastic stroma within the tumor microenvironment (TME), contributes to an unfavorable prognosis. The mechanisms and consequences of interactions among different cell types, along with spatial variations influencing cellular function, potentially play a role in the pathogenesis of PDAC. Understanding the diverse compositions of the TME and elucidating the functions of microscopic neighborhoods may contribute to understanding the immune microenvironment status in pancreatic cancer. As we delve into the spatial biology of the microscopic neighborhoods within the TME, aiding in deciphering the factors that orchestrate this intricate ecosystem. This overview delineates the fundamental constituents and the structural arrangement of the PDAC microenvironment, highlighting their impact on cancer cell biology.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":"1561-1578"},"PeriodicalIF":6.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: EMP2 induces cytostasis and apoptosis via the TGFβ/SMAD/SP1 axis and recruitment of P2RX7 in urinary bladder urothelial carcinoma.","authors":"Chien-Feng Li, Ti-Chun Chan, Cheng-Tang Pan, Pichpisith Pierre Vejvisithsakul, Jia-Chen Lai, Szu-Yu Chen, Ya-Wen Hsu, Meng-Shin Shiao, Yow-Ling Shiue","doi":"10.1007/s13402-024-00985-z","DOIUrl":"10.1007/s13402-024-00985-z","url":null,"abstract":"","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":"2015-2017"},"PeriodicalIF":6.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research advances in the molecular classification of gastric cancer.","authors":"Dike Shi, Zihan Yang, Yanna Cai, Hongbo Li, Lele Lin, Dan Wu, Shengyu Zhang, Qingqu Guo","doi":"10.1007/s13402-024-00951-9","DOIUrl":"10.1007/s13402-024-00951-9","url":null,"abstract":"<p><p>Gastric cancer (GC) is a malignant tumor with one of the lowest five-year survival rates. Traditional first-line treatment regimens, such as platinum drugs, have limited therapeutic efficacy in treating advanced GC and significant side effects, greatly reducing patient quality of life. In contrast, trastuzumab and other immune checkpoint inhibitors, such as nivolumab and pembrolizumab, have demonstrated consistent and reliable efficacy in treating GC. Here, we discuss the intrinsic characteristics of GC from a molecular perspective and provide a comprehensive review of classification and treatment advances in the disease. Finally, we suggest several strategies based on the intrinsic molecular characteristics of GC to aid in overcoming clinical challenges in the development of precision medicine and improve patient prognosis.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":"1523-1536"},"PeriodicalIF":6.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875966","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":"Deciphering the molecular landscape: evolutionary progression from gynecomastia to aggressive male breast cancer.","authors":"Chuang Yang, Zhonglin Wang, Lijun Qian, Jingyue Fu, Handong Sun","doi":"10.1007/s13402-024-00964-4","DOIUrl":"10.1007/s13402-024-00964-4","url":null,"abstract":"<p><strong>Background: </strong>Gynecomastia denotes the benign proliferation of glandular breast tissue and stands as a recognized risk factor for male breast cancer. Nonetheless, the underlying carcinogenic mechanisms orchestrating the progression from gynecomastia to cancer remain poorly understood.</p><p><strong>Methods: </strong>This study employed single-cell RNA sequencing (scRNA-seq) to meticulously dissect the cellular landscape of gynecomastia and unravel potential associations with male breast cancer at a single-cell resolution. Pseudotime and evolutionary analyses were executed to delineate the distinct features characterizing gynecomastia and male breast cancer. The TCGA database, along with cell-cell communication analysis and immunohistochemistry staining, was harnessed to validate differential gene expression, specifically focusing on CD13.</p><p><strong>Result: </strong>From the copy number variation profiles and evolutionary tree, we inferred shared mutation characteristics (18p⁺ and 18q⁺) underpinning both conditions. The developmental trajectory unveiled an intriguing overlap between gynecomastia and malignant epithelial cells. Moreover, the differential gene CD13 emerged as a common denominator in both gynecomastia and male breast cancer when compared with normal mammary tissue. Cell-cell interaction analysis and communication dynamics within the tumor microenvironment spotlighted distinctions between CD13⁺ and CD13^- subsets, with the former exhibiting elevated expression of FGFR1-FGF7.</p><p><strong>Conclusions: </strong>Our investigation provides novel insights into the evolutionary progression from gynecomastia to male breast cancer, shedding light on the pivotal role of CD13 in driving this transition. The identification of CD13 as a potential therapeutic target suggests the feasibility of CD13-targeted interventions, specifically tailored for male breast cancer treatment.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":"1831-1843"},"PeriodicalIF":6.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The PPP2R1A cancer hotspot mutant p.R183W increases clofarabine resistance in uterine serous carcinoma cells by a gain-of-function mechanism.","authors":"Michiel Remmerie, Rüveyda Dok, Zhigang Wang, Judit Domènech Omella, Sophie Alen, Célie Cokelaere, Lisa Lenaerts, Erwin Dreesen, Sandra Nuyts, Rita Derua, Veerle Janssens","doi":"10.1007/s13402-024-00963-5","DOIUrl":"10.1007/s13402-024-00963-5","url":null,"abstract":"<p><strong>Purpose: </strong>Uterine serous carcinoma (USC) is generally associated with poor prognosis due to a high recurrence rate and frequent treatment resistance; hence, there is a need for improved therapeutic strategies. Molecular analysis of USC identified several molecular markers, useful to improve current treatments or identify new druggable targets. PPP2R1A, encoding the Aα subunit of the tumor suppressive Ser/Thr phosphatase PP2A, is mutated in up to 40% of USCs. Here, we investigated the effect of the p.R183W PPP2R1A hotspot variant on treatment response to the nucleoside analogue clofarabine.</p><p><strong>Methods and results: </strong>USC cells stably expressing p.R183W Aα showed increased resistance to clofarabine treatment in vitro and, corroborated by decreased clofarabine-induced apoptosis, G1 phase arrest, DNA-damage (γH2AX) and activation of ATM and Chk1/2 kinases. Phenotypic rescue by pharmacologic PP2A inhibition or dicer-substrate siRNA (dsiRNA)-mediated B56δ subunit knockdown supported a gain-of-function mechanism of Aα p.R183W, promoting dephosphorylation and inactivation of deoxycytidine kinase (dCK), the cellular enzyme responsible for the conversion of clofarabine into its bioactive form. Therapeutic assessment of related nucleoside analogues (gemcitabine, cladribine) revealed similar effects, but in a cell line-dependent manner. Expression of two other PPP2R1A USC mutants (p.P179R or p.S256F) did not affect clofarabine response in our cell models, arguing for mutant-specific effects on treatment outcome as well.</p><p><strong>Conclusions: </strong>While our results call for PPP2R1A mutant and context-dependent effects upon clofarabine/nucleoside analogue monotherapy, combining clofarabine with a pharmacologic PP2A inhibitor proved synergistically in all tested conditions, highlighting a new generally applicable strategy to improve treatment outcome in USC.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":"1811-1829"},"PeriodicalIF":6.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circadian system disorder induced by aberrantly activated EFNB2-EPHB2 axis leads to facilitated liver metastasis in gastric cancer","authors":"Qing Li, Yuxuan Lin, Bo Ni, Haigang Geng, Chaojie Wang, Enhao Zhao, Chunchao Zhu","doi":"10.1007/s13402-024-00991-1","DOIUrl":"https://doi.org/10.1007/s13402-024-00991-1","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Liver is one of the most preferred destinations for distant metastasis of gastric cancer (GC) and liver metastasis usually predicts poor prognosis. The achievement of liver metastasis requires continued cross-talk of complex members in tumor microenvironment (TME) including tumor associated macrophages (TAMs).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Results from 35 cases of ex vivo cultured living tissues of GC liver metastasis have elucidated that circadian rhythm disorder (CRD) of key molecules involved in circadian timing system (CTS) facilitates niche outgrowth. We next analyzed 69 cases of liver metastasis from patients bearing GC and designed co-culture or 3D cell culture, discovering that TAMs expressing EFNB2 could interact with tumor cell expressing EPHB2 for forward downstream signaling and lead to CRD of tumor cells. Moreover, we performed intrasplenic injection models assessed by CT combined 3D organ reconstruction bioluminescence imaging to study liver metastasis and utilized the clodronate treatment, bone marrow transplantation or EPH inhibitor for in vivo study followed by exploring the clinical therapeutic value of which in patient derived xenograft (PDX) mouse model.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Ex vivo studies demonstrated that CRD of key CTS molecules facilitates niche outgrowth in liver metastases. In vitro studies revealed that TAMs expressing EFNB2 interact with tumor cells expressing EPHB2, leading to CRD and downstream signaling activation. The underlying mechanism is the enhancement of the Warburg effect in metastatic niches.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Overall, we aim to uncover the mechanism in TAMs induced CRD which promotes liver metastasis of GC and provide novel ideas for therapeutic strategies.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":"39 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}