Depletion of Carcinoma-Associated Fibroblasts and Fibrosis Induces Immunosuppression and Accelerates Pancreas Cancer with Reduced Survival.
Berna C. Özdemir,Berna C. Özdemir,Tsvetelina Pentcheva-Hoang,Julienne L. Carstens,Xiaofeng Zheng,Chia Chin Wu,Tyler R. Simpson,Hanane Laklai,Hikaru Sugimoto,Hikaru Sugimoto,Christoph Kahlert,Christoph Kahlert,Sergey V. Novitskiy,Ana De Jesus-Acosta,Padmanee Sharma,Pedram Heidari,Umar Mahmood,Lynda Chin,Harold L. Moses,Valerie M. Weaver,Anirban Maitra,James P. Allison,Valerie S. LeBleu,Valerie S. LeBleu,Raghu Kalluri,Raghu Kalluri +25 more
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TLDR
Although myofibroblast-depleted tumors did not respond to gemcitabine, anti-CTLA4 immunotherapy reversed disease acceleration and prolonged animal survival, and underscores the need for caution in targeting carcinoma-associated fibroblasts in PDAC.About:
This article is published in Cancer Cell.The article was published on 2014-06-16 and is currently open access. It has received 1835 citations till now. The article focuses on the topics: Pancreatic cancer & Cancer stem cell.read more
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The biology and function of fibroblasts in cancer
TL;DR: Cancer-associated fibroblasts (CAFs) become synthetic machines that produce many different tumour components and have a role in creating extracellular matrix structure and metabolic and immune reprogramming of the tumour microenvironment with an impact on adaptive resistance to chemotherapy.
Journal ArticleDOI
Glypican-1 identifies cancer exosomes and detects early pancreatic cancer
Sonia A. Melo,Linda B. Luecke,Christoph Kahlert,Agustín F. Fernández,Seth T. Gammon,Judith Kaye,Valerie S. LeBleu,Elizabeth A. Mittendorf,Juergen Weitz,Nuh N. Rahbari,Christoph Reissfelder,Christian Pilarsky,Mario F. Fraga,David Piwnica-Worms,Raghu Kalluri +14 more
TL;DR: GPC1+ crExos may serve as a potential non-invasive diagnostic and screening tool to detect early stages of pancreatic cancer to facilitate possible curative surgical therapy.
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Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer
Xiaofeng Zheng,Julienne L. Carstens,Jiha Kim,Matthew Scheible,Judith Kaye,Hikaru Sugimoto,Chia Chin Wu,Valerie S. LeBleu,Raghu Kalluri +8 more
TL;DR: This study functionally probes the role of EMT in PDAC by generating mouse models of PDAC with deletion of Snail or Twist, two key transcription factors responsible for EMT, and highlights the importance of combining EMT inhibition with chemotherapy for the treatment of pancreatic cancer.
Journal ArticleDOI
A framework for advancing our understanding of cancer-associated fibroblasts
Erik Sahai,Igor Astsaturov,Edna Cukierman,David G. DeNardo,Mikala Egeblad,Ronald M. Evans,Ronald M. Evans,Douglas T. Fearon,Douglas T. Fearon,Florian R. Greten,Sunil R. Hingorani,Tony Hunter,Richard O. Hynes,Rakesh K. Jain,Tobias Janowitz,Claus Jørgensen,Alec C. Kimmelman,Mikhail G. Kolonin,Robert G. Maki,Robert G. Maki,R. Scott Powers,Ellen Puré,Daniel C. Ramirez,Ruth Scherz-Shouval,Mara H. Sherman,Sheila A. Stewart,Thea D. Tlsty,David A. Tuveson,Fiona M. Watt,Valerie M. Weaver,Ashani T. Weeraratna,Zena Werb +31 more
TL;DR: This Consensus Statement issues a call to action for all cancer researchers to standardize assays and report metadata in studies of cancer-associated fibroblasts to advance the understanding of this important cell type in the tumour microenvironment.
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Inflammation and Cancer: Triggers, Mechanisms, and Consequences.
TL;DR: How tumor-promoting inflammation closely resembles inflammatory processes typically found during development, immunity, maintenance of tissue homeostasis, or tissue repair is discussed and the distinctions between tissue-protective and pro-tumorigenic inflammation are illuminated.
References
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Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.
TL;DR: By following this protocol, investigators are able to gain an in-depth understanding of the biological themes in lists of genes that are enriched in genome-scale studies.
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Inflammation and cancer
Lisa M. Coussens,Zena Werb +1 more
TL;DR: It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration.
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The basics of epithelial-mesenchymal transition
Raghu Kalluri,Robert A. Weinberg +1 more
TL;DR: Processes similar to the EMTs associated with embryo implantation, embryogenesis, and organ development are appropriated and subverted by chronically inflamed tissues and neoplasias and the identification of the signaling pathways that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes.
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The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells
Sendurai A. Mani,Wenjun Guo,Mai Jing Liao,Elinor Ng Eaton,Ayyakkannu Ayyanan,Alicia Y. Zhou,Mary W. Brooks,Ferenc Reinhard,Cheng Cheng Zhang,Michail Shipitsin,Lauren L. Campbell,Kornelia Polyak,Cathrin Brisken,Jing Yang,Robert A. Weinberg +14 more
TL;DR: It is reported that the induction of an EMT in immortalized human mammary epithelial cells (HMLEs) results in the acquisition of mesenchymal traits and in the expression of stem-cell markers, and it is shown that those cells have an increased ability to form mammospheres, a property associated with mammARY epithelial stem cells.
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