Mahsa Pahlavan, Weikun Xiao, F. Eun, C. Hwang, R. Hill
{"title":"Abstract PO-123: Development of a 3D biomimetic metastatic liver niche model for pancreatic cancer","authors":"Mahsa Pahlavan, Weikun Xiao, F. Eun, C. Hwang, R. Hill","doi":"10.1158/1538-7445.panca21-po-123","DOIUrl":"https://doi.org/10.1158/1538-7445.panca21-po-123","url":null,"abstract":"","PeriodicalId":92311,"journal":{"name":"Tumor & microenvironment","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79956771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenting Du, Rosa E. Menjivar, Katelyn L. Donahue, Ashley Velez-Delgado, M. Pasca di Magliano
{"title":"Abstract PO-104: Activation of WNT signaling in CD4+ T cells promotes immune suppression in pancreatic cancer","authors":"Wenting Du, Rosa E. Menjivar, Katelyn L. Donahue, Ashley Velez-Delgado, M. Pasca di Magliano","doi":"10.1158/1538-7445.panca21-po-104","DOIUrl":"https://doi.org/10.1158/1538-7445.panca21-po-104","url":null,"abstract":"","PeriodicalId":92311,"journal":{"name":"Tumor & microenvironment","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88132928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Y. Dou, Wesley J. Hunt, Justin Chhuor, F. Taghizadeh, Atefeh Samani, Karnjit Sarai, C. Dubois, D. Schaeffer, M. Sander, Janel L. Kopp
{"title":"Abstract PO-103: Cellular origin influences immune microenvironment in a pancreatic cancer mouse model with loss of Pten and activation of Kras","authors":"Y. Dou, Wesley J. Hunt, Justin Chhuor, F. Taghizadeh, Atefeh Samani, Karnjit Sarai, C. Dubois, D. Schaeffer, M. Sander, Janel L. Kopp","doi":"10.1158/1538-7445.panca21-po-103","DOIUrl":"https://doi.org/10.1158/1538-7445.panca21-po-103","url":null,"abstract":"","PeriodicalId":92311,"journal":{"name":"Tumor & microenvironment","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88282474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
B. Kinny-Köster, Melissa R Lyman, Dimitri N. Sidiropoulos, Melanie Loth, Alexandra B. Puscek, L. Wood, Jin He, Jun Yu, R. Burkhart, E. Jaffee, Jacquelyn W. Zimmerman, E. Fertig
{"title":"Abstract PO-111: A human single-cell RNA sequencing atlas of pancreatic ductal adenocarcinoma enables harmonized cell type calling and comprehensive analyses of potential intercellular signaling","authors":"B. Kinny-Köster, Melissa R Lyman, Dimitri N. Sidiropoulos, Melanie Loth, Alexandra B. Puscek, L. Wood, Jin He, Jun Yu, R. Burkhart, E. Jaffee, Jacquelyn W. Zimmerman, E. Fertig","doi":"10.1158/1538-7445.panca21-po-111","DOIUrl":"https://doi.org/10.1158/1538-7445.panca21-po-111","url":null,"abstract":"","PeriodicalId":92311,"journal":{"name":"Tumor & microenvironment","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83205174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Barbara T. Grünwald, Curtis W. McCloskey, A. Devisme, F. Vyas, G. Andrieux, Kazeera Aliar, F. Notta, G. O’Kane, Julie M. Wilson, Julia Knox, S. Fischer, T. Kislinger, M. Boerries, S. Gallinger, R. Khokha
{"title":"Abstract PO-107: Fibroblast differentiation trajectories elicit regional tissue states in pancreatic cancer","authors":"Barbara T. Grünwald, Curtis W. McCloskey, A. Devisme, F. Vyas, G. Andrieux, Kazeera Aliar, F. Notta, G. O’Kane, Julie M. Wilson, Julia Knox, S. Fischer, T. Kislinger, M. Boerries, S. Gallinger, R. Khokha","doi":"10.1158/1538-7445.panca21-po-107","DOIUrl":"https://doi.org/10.1158/1538-7445.panca21-po-107","url":null,"abstract":"Intratumoral heterogeneity is a critical frontier in understanding how the tumor microenvironment (TME) propels malignant progression. We recently deconvoluted regional heterogeneity in the human PDAC stroma to assess its role in disease progression and discovered two types of ‘sub-tumor microenvironments’ (subTMEs), called ‘reactive’ and ‘deserted’. These histologically definable tissue states exhibit strong regional relationships with tumor immunity, subtypes, differentiation, and treatment response. Here, we set out to define their cell biological underpinnings through a combination of subTME-specific cancer-associated fibroblast (CAF) models, integrative histopathology, quantitative image analysis, multiOMICs, scRNAseq, and controlled functional assays. Remarkably, the growth patterns of CAF cultures closely recapitulated the characteristic histomorphology of their originating subTMEs, and these distinct phenotypes were accompanied by behavioral differences. Unsupervised graph-based clustering of scRNAseq profiles showed that CAFs largely grouped by their originating subTME yet comprised up to 10 individual clusters. The subTME-specific multi-subpopulation CAF communities self-organized into distinct ‘coordinated states’, represented by cluster-overarching functional profiles and distinct morpho-histological and behavioral phenotypes. These differences originated in cellular differentiation trajectories, with an ‘intermediate’ transitory state evident both in single cell transcriptomics and in situ. Noticeably, this CAF differentiation potential was associated with distinct tumor-related functions and, similar to stem cells, was marked by RNA diversity and pluripotency markers. Therefore, regional TME programs in PDAC appear to result largely from transitions between subpopulation-overarching fibroblast differentiation states that guide multifaceted CAF and immune cell communities into recurrent tissue self-organizational units. Citation Format: Barbara T. Grunwald, Curtis McCloskey, Antoine Devisme, Foram Vyas, Geoffroy Andrieux, Kazeera Aliar, Faiyaz Notta, Grainne O’Kane, Julie Wilson, Jennifer Knox, Sandra Fischer, Thomas Kislinger, Melanie Boerries, Steven Gallinger, Rama Khokha. Fibroblast differentiation trajectories elicit regional tissue states in pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-107.","PeriodicalId":92311,"journal":{"name":"Tumor & microenvironment","volume":"348 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76158669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rosa E. Menjivar, Z. Nwosu, Wenting Du, Katelyn L. Donahue, Carlos E Espinoza, Ashley Velez-Delgado, Kristee L Brown, Wei Yan, Christopher J. Halbrook, Yaqing Zhang, Costas Lyssiotis, M. Pasca di Magliano
{"title":"Abstract PO-116: Deletion of Arginase 1 in myeloid cells alters the pancreatic cancer microenvironment","authors":"Rosa E. Menjivar, Z. Nwosu, Wenting Du, Katelyn L. Donahue, Carlos E Espinoza, Ashley Velez-Delgado, Kristee L Brown, Wei Yan, Christopher J. Halbrook, Yaqing Zhang, Costas Lyssiotis, M. Pasca di Magliano","doi":"10.1158/1538-7445.panca21-po-116","DOIUrl":"https://doi.org/10.1158/1538-7445.panca21-po-116","url":null,"abstract":"","PeriodicalId":92311,"journal":{"name":"Tumor & microenvironment","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76304943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Identification and Characterization of Glycine Decarboxylase as a Direct Target of Snail in the Epithelial-Mesenchymal Transition of Cancer Cells.","authors":"Guohua Chen, Jianmei Wu, Jing Li, Jian Wang","doi":"10.4103/tme.tme_8_18","DOIUrl":"https://doi.org/10.4103/tme.tme_8_18","url":null,"abstract":"<p><strong>Context/aims: </strong>Metabolic reprogramming and cellular plasticity drive tumorigenesis. However, how these cellular events collectively contribute to the oncogenic process is poorly understood. Epithelial-mesenchymal transition (EMT), a fundamental mechanism of cellular plasticity, is governed by the EMT transcription repressors such as Snail. In the present study, through establishment and characterization of inducible overexpression of Snail in A549 lung cancer cells, we aim to define the metabolic reprogramming in response to Snail in the EMT of lung cancer cells.</p><p><strong>Methods/results: </strong>Our metabolomic analysis suggests that forced expression of Snail accompanied reduced diversion of glycolytic metabolites to the serine/glycine metabolic shunt, a critical metabolic branch that distributes glucose catabolic intermediates to the major anabolic pathways. Our gene expression profiling and molecular characterization revealed that Snail actively suppressed the expression of glycine decarboxylase (GLDC), a key enzyme on the serine/glycine metabolic shunt, through binding to an evolutionarily conserved E-box motif and thereby inhibiting the promoter of the GLDC gene. Besides, knockdown of GLDC led to a cellular function shift from proliferation to migration.</p><p><strong>Conclusion: </strong>This study has revealed a novel molecular link that integrates the serine/glycine metabolism with the Snail-mediated EMT program in cancer cells.</p>","PeriodicalId":92311,"journal":{"name":"Tumor & microenvironment","volume":"1 2","pages":"55-62"},"PeriodicalIF":0.0,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38819203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tumor Microenvironment: The Role of Chemokines – Part B","authors":"","doi":"10.1007/978-3-030-62658-7","DOIUrl":"https://doi.org/10.1007/978-3-030-62658-7","url":null,"abstract":"","PeriodicalId":92311,"journal":{"name":"Tumor & microenvironment","volume":"65 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91084444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}