Cancer Science最新文献_第6页

Decreased PU.1 expression in mature B cells induces lymphomagenesis. 成熟 B 细胞中 PU.1 表达减少会诱发淋巴瘤。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-09-25 DOI: 10.1111/cas.16344

Shinya Endo, Nao Nishimura, Kosuke Toyoda, Yoshihiro Komohara, Joaquim Carreras, Hiromichi Yuki, Takafumi Shichijo, Shikiko Ueno, Niina Ueno, Shinya Hirata, Yawara Kawano, Kisato Nosaka, Masashi Miyaoka, Naoya Nakamura, Ai Sato, Kiyoshi Ando, Hiroaki Mitsuya, Koichi Akashi, Daniel G Tenen, Jun-Ichirou Yasunaga, Masao Matsuoka, Yutaka Okuno, Hiro Tatetsu

{"title":"Decreased PU.1 expression in mature B cells induces lymphomagenesis.","authors":"Shinya Endo, Nao Nishimura, Kosuke Toyoda, Yoshihiro Komohara, Joaquim Carreras, Hiromichi Yuki, Takafumi Shichijo, Shikiko Ueno, Niina Ueno, Shinya Hirata, Yawara Kawano, Kisato Nosaka, Masashi Miyaoka, Naoya Nakamura, Ai Sato, Kiyoshi Ando, Hiroaki Mitsuya, Koichi Akashi, Daniel G Tenen, Jun-Ichirou Yasunaga, Masao Matsuoka, Yutaka Okuno, Hiro Tatetsu","doi":"10.1111/cas.16344","DOIUrl":"https://doi.org/10.1111/cas.16344","url":null,"abstract":"Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of lymphoma, accounting for 30% of non-Hodgkin lymphomas. Although comprehensive analysis of genetic abnormalities has led to the classification of lymphomas, the exact mechanism of lymphomagenesis remains elusive. The Ets family transcription factor, PU.1, encoded by Spi1, is essential for the development of myeloid and lymphoid cells. Our previous research illustrated the tumor suppressor function of PU.1 in classical Hodgkin lymphoma and myeloma cells. In the current study, we found that patients with DLBCL exhibited notably reduced PU.1 expression in their lymphoma cells, particularly in the non-germinal center B-cell-like (GCB) subtype. This observation suggests that downregulation of PU.1 may be implicated in DLBCL tumor growth. To further assess PU.1's role in mature B cells in vivo, we generated conditional Spi1 knockout mice using Cγ1-Cre mice. Remarkably, 13 of the 23 knockout mice (56%) showed splenomegaly, lymphadenopathy, or masses, with some having histologically confirmed B-cell lymphomas. In contrast, no wild-type mice developed B-cell lymphoma. In addition, RNA-seq analysis of lymphoma cells from Cγ1-Cre Spi1F/F mice showed high frequency of each monoclonal CDR3 sequence, indicating that these lymphoma cells were monoclonal tumor cells. When these B lymphoma cells were transplanted into immunodeficient recipient mice, all mice died within 3 weeks. Lentiviral-transduced Spi1 rescued 60% of the recipient mice, suggesting that PU.1 has a tumor suppressor function in vivo. Collectively, PU.1 is a tumor suppressor in mature B cells, and decreased PU.1 results in mature B-cell lymphoma development.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330532","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}

引用次数: 0

Host ANGPTL2 establishes an immunosuppressive tumor microenvironment and resistance to immune checkpoint therapy. 宿主 ANGPTL2 可建立免疫抑制性肿瘤微环境，并对免疫检查点疗法产生抗药性。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-09-25 DOI: 10.1111/cas.16348

Shinsei Yumoto, Haruki Horiguchi, Tsuyoshi Kadomatsu, Taichi Horino, Michio Sato, Kazutoyo Terada, Keishi Miyata, Toshiro Moroishi, Hideo Baba, Yuichi Oike

{"title":"Host ANGPTL2 establishes an immunosuppressive tumor microenvironment and resistance to immune checkpoint therapy.","authors":"Shinsei Yumoto, Haruki Horiguchi, Tsuyoshi Kadomatsu, Taichi Horino, Michio Sato, Kazutoyo Terada, Keishi Miyata, Toshiro Moroishi, Hideo Baba, Yuichi Oike","doi":"10.1111/cas.16348","DOIUrl":"https://doi.org/10.1111/cas.16348","url":null,"abstract":"Use of immune checkpoint inhibitors (ICIs) as cancer immunotherapy has advanced rapidly in the clinic; however, mechanisms underlying resistance to ICI therapy, including impaired T cell infiltration, low immunogenicity, and tumor \"immunophenotypes\" governed by the host, remain unclear. We previously reported that in some cancer contexts, tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) has tumor-promoting functions. Here, we asked whether ANGPTL2 deficiency could enhance antitumor ICI activity in two inflammatory contexts: a murine syngeneic model of colorectal cancer and a mouse model of high-fat diet (HFD)-induced obesity. Systemic ANGPTL2 deficiency potentiated ICI efficacy in the syngeneic model, supporting an immunosuppressive role for host ANGPTL2. Relevant to the mechanism, we found that ANGPTL2 induces pro-inflammatory cytokine production in adipose tissues, driving generation of myeloid-derived suppressor cells (MDSCs) in bone marrow and contributing to an immunosuppressive tumor microenvironment and resistance to ICI therapy. Moreover, HFD-induced obese mice showed impaired responsiveness to ICI treatment, suggesting that obesity-induced chronic inflammation facilitated by high ANGPTL2 expression blocks ICI antitumor effects. Our findings overall provide novel insight into protumor ANGPTL2 functions and illustrate the essential role of the host system in ICI responsiveness.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330534","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}

引用次数: 0

Anti-tissue factor antibody conjugated with monomethyl auristatin E or deruxtecan in pancreatic cancer models. 在胰腺癌模型中使用与单甲基金丝桃素 E 或德鲁替康结合的抗组织因子抗体。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-09-25 DOI: 10.1111/cas.16335

Ryo Tsumura, Takahiro Anzai, Yoshikatsu Koga, Hiroki Takashima, Yasuhiro Matsumura, Masahiro Yasunaga

{"title":"Anti-tissue factor antibody conjugated with monomethyl auristatin E or deruxtecan in pancreatic cancer models.","authors":"Ryo Tsumura, Takahiro Anzai, Yoshikatsu Koga, Hiroki Takashima, Yasuhiro Matsumura, Masahiro Yasunaga","doi":"10.1111/cas.16335","DOIUrl":"https://doi.org/10.1111/cas.16335","url":null,"abstract":"Antibody-drug conjugates (ADCs) have been recognized as a promising class of cancer therapeutics. Tissue factor (TF), an initiator of the blood coagulation pathway, has been investigated regarding its relationship with cancer, and several preclinical and clinical studies have presented data on anti-TF ADCs, including tisotumab vedotin, which was approved in 2021. However, the feasibility of other payloads in the design of anti-TF ADCs is still unclear because no reports have compared payloads with different cytotoxic mechanisms. For ADCs targeting other antigens, such as Her2, optimizing the payload is also an important issue in order to improve in vivo efficacy. In this study, we prepared humanized anti-TF Ab (clone.1084) conjugated with monomethyl auristatin E (MMAE) or deruxtecan (DXd), and evaluated the efficacy in several cell line- and patient-derived xenograft models of pancreatic cancer. As a result, optimizing the drug / Ab ratio was necessary for each payload in order to prevent pharmacokinetic deterioration and maximize delivery efficiency. In addition, MMAE-conjugated anti-TF ADC showed higher antitumor effects in tumors with strong and homogeneous TF expression, while DXd-conjugated anti-TF ADC was more effective in tumors with weak and heterogeneous TF expression. Analysis of a pancreatic cancer tissue array showed weak and heterogeneous TF expression in most TF-positive specimens, indicating that the response rate to pancreatic cancer might be higher for DXd- than MMAE-conjugated anti-TF ADC. Nevertheless, our findings indicated that optimizing the ADC payloads individually in each patient could maximize the potential of ADC therapeutics.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330530","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}

引用次数: 0

BBOX1-AS1 promotes gastric cardia adenocarcinoma progression via interaction with CtBP2 to facilitate the epithelial-mesenchymal transition process. BBOX1-AS1通过与CtBP2相互作用促进上皮-间质转化过程，从而促进胃贲门腺癌的进展。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-09-24 DOI: 10.1111/cas.16350

Wenxu Zou, Qing Yin, Wei Guo, Zhiming Dong, Yanli Guo

{"title":"BBOX1-AS1 promotes gastric cardia adenocarcinoma progression via interaction with CtBP2 to facilitate the epithelial-mesenchymal transition process.","authors":"Wenxu Zou, Qing Yin, Wei Guo, Zhiming Dong, Yanli Guo","doi":"10.1111/cas.16350","DOIUrl":"https://doi.org/10.1111/cas.16350","url":null,"abstract":"It is recognized that lncRNA BBOX1-AS1 exerts a crucial oncogenic property in several cancer types. However, the functions and underlying mechanisms of BBOX1-AS1 in the epithelial-mesenchymal transition (EMT) process of gastric cardia adenocarcinoma (GCA) have remained unclarified. The findings of this study demonstrated that GCA tissues had elevated BBOX1-AS1 expression levels, which was associated with a worse prognosis in GCA patients. BBOX1-AS1 dramatically enhanced cell proliferation, invasion, and TGF-β1-induced the EMT process in vitro. Further mechanism analysis revealed that BBOX1-AS1 could combine with CtBP2 and strengthen the interaction of CtBP2 and ZEB1. BBOX1-AS1 might regulate the E-cadherin expression through CtBP2/ZEB1 transcriptional complex-mediated transcriptional repression, further affecting the activation of the Wnt/β-catenin pathway and the EMT process. Overall, our findings demonstrate that BBOX1-AS1 might act as an lncRNA associated with EMT for facilitating GCA advancement via interaction with CtBP2 to facilitate the activation of Wnt/β-catenin pathway and the EMT process, which indicated that it might function as an exploitable treatment target for GCA patients.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330531","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}

引用次数: 0

Correction to "Expression of concern: Hydroxychavicol, a Piper betle leaf component, induces apoptosis of CML cells through mitochondrial reactive oxygen species-dependent JNK and endothelial nitric oxide synthase activation and overrides imatinib resistance". 对 "表达关切：胡椒槟榔叶成分羟基黄烷醇通过线粒体活性氧依赖性 JNK 和内皮一氧化氮合酶激活诱导 CML 细胞凋亡，并克服伊马替尼耐药性 "的更正。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-09-23 DOI: 10.1111/cas.16357

引用次数: 0

Orosomucoid 2 upregulation mediates liver injury-induced colorectal cancer liver metastasis by promoting EMT and cell migration. Orosomucoid 2上调通过促进EMT和细胞迁移介导肝损伤诱导的结直肠癌肝转移。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-03-12 DOI: 10.1111/cas.16131

Xundong Wei, Lei Wang, Bing Yang, Yuanyuan Ma, Wei Yuan, Jie Ma

{"title":"Orosomucoid 2 upregulation mediates liver injury-induced colorectal cancer liver metastasis by promoting EMT and cell migration.","authors":"Xundong Wei, Lei Wang, Bing Yang, Yuanyuan Ma, Wei Yuan, Jie Ma","doi":"10.1111/cas.16131","DOIUrl":"https://doi.org/10.1111/cas.16131","url":null,"abstract":"The relationship between drug-induced liver injury and liver metastasis of colorectal cancer and the underlying mechanisms are not well understood. In this study, we used carbon tetrachloride to construct a classic mouse liver injury model and injected CT26 colorectal cancer cells into the mouse spleen to simulate the natural route of colorectal cancer liver metastasis. Liver injury significantly increased the number of colorectal cancer liver metastases. Transcriptome sequencing and data-independent acquisition protein quantification identified proteins that were significantly differentially expressed in injured livers, and orosomucoid (ORM) 2 was identified as a target protein for tumor liver metastasis. In vitro experiments showed that exogenous ORM2 protein increased the expression of EMT markers such as Twist, Zeb1, Vim, Snail1 and Snail2 and chemokine ligands to promote CT26 cell migration. In addition, liver-specific overexpression of the ORM2 protein in the mouse model significantly promoted tumor cell liver metastasis without inducing liver injury. Our results indicate that drug-induced liver injury can promote colorectal cancer liver metastasis and that ORM2 can promote cell migration by inducing EMT in tumor cells.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140111933","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}

引用次数: 0