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Cancer-Associated F...
Cancer-Associated Fibroblasts and Squamous Epithelial Cells Constitute a Unique Microenvironment in a Mouse Model of Inflammation-Induced Colon Cancer
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- Vega, Paige N. (författare)
- Vanderbilt University
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- Nilsson, Avlant, 1985 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology,Massachusetts Institute of Technology (MIT)
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- Kumar, Manu P. (författare)
- Massachusetts Institute of Technology (MIT)
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- Niitsu, Hiroaki (författare)
- Vanderbilt University
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- Simmons, Alan J. (författare)
- Vanderbilt University
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- Ro, James (författare)
- Vanderbilt University
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- Wang, Jiawei (författare)
- Vanderbilt University
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- Chen, Zhengyi (författare)
- Vanderbilt University
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- Joughin, Brian A. (författare)
- Massachusetts Institute of Technology (MIT)
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- Li, Wei (författare)
- Vanderbilt University
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- McKinley, Eliot T. (författare)
- Vanderbilt University
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- Liu, Qi (författare)
- Vanderbilt University
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- Roland, Joseph T. (författare)
- Vanderbilt University
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- Washington, M. Kay (författare)
- Vanderbilt University
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- Coffey, Robert J. (författare)
- Vanderbilt University
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- Lauffenburger, Douglas A. (författare)
- Massachusetts Institute of Technology (MIT)
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- Lau, Ken S. (författare)
- Vanderbilt University
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(creator_code:org_t)
- 2022-05-04
- 2022
- Engelska.
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Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 12
- Relaterad länk:
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https://research.cha... (primary) (free)
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https://doi.org/10.3...
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https://research.cha...
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Abstract
Ämnesord
Stäng
- The tumor microenvironment plays a key role in the pathogenesis of colorectal tumors and contains various cell types including epithelial, immune, and mesenchymal cells. Characterization of the interactions between these cell types is necessary for revealing the complex nature of tumors. In this study, we used single-cell RNA-seq (scRNA-seq) to compare the tumor microenvironments between a mouse model of sporadic colorectal adenoma (Lrig1(CreERT2/+);Apc(2lox14/+)) and a mouse model of inflammation-driven colorectal cancer induced by azoxymethane and dextran sodium sulfate (AOM/DSS). While both models develop tumors in the distal colon, we found that the two tumor types have distinct microenvironments. AOM/DSS tumors have an increased abundance of two populations of cancer-associated fibroblasts (CAFs) compared with APC tumors, and we revealed their divergent spatial association with tumor cells using multiplex immunofluorescence (MxIF) imaging. We also identified a unique squamous cell population in AOM/DSS tumors, whose origins were distinct from anal squamous epithelial cells. These cells were in higher proportions upon administration of a chemotherapy regimen of 5-Fluorouracil/Irinotecan. We used computational inference algorithms to predict cell-cell communication mediated by ligand-receptor interactions and downstream pathway activation, and identified potential mechanistic connections between CAFs and tumor cells, as well as CAFs and squamous epithelial cells. This study provides important preclinical insight into the microenvironment of two distinct models of colorectal tumors and reveals unique roles for CAFs and squamous epithelial cells in the AOM/DSS model of inflammation-driven cancer.
Ämnesord
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Nyckelord
- stem cells
- tumor microenvironment
- cancer associated fibroblasts (CAF)
- inflammation
- squamous cells
- colorectal cancer
- adaptive immunity
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Vega, Paige N.
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Nilsson, Avlant, ...
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Kumar, Manu P.
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Niitsu, Hiroaki
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Simmons, Alan J.
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Ro, James
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visa fler...
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Wang, Jiawei
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Chen, Zhengyi
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Joughin, Brian A ...
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Li, Wei
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McKinley, Eliot ...
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Liu, Qi
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Roland, Joseph T ...
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Washington, M. K ...
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Coffey, Robert J ...
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Lauffenburger, D ...
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Lau, Ken S.
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visa färre...
- Om ämnet
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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och Cellbiologi
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Cell och molekyl ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Immunologi inom ...
- Artiklar i publikationen
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Frontiers in Onc ...
- Av lärosätet
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Chalmers tekniska högskola