PDAC (pancreatic ductal adenocarcinoma) is among the most deadly of human malignances. A hallmark of the disease is a pronounced collagen-rich fibrotic extracellular matrix known as the desmoplastic reaction. Intriguingly, it is precisely these areas of fibrosis in which human PDAC tumours demonstrate increased expression of a key collagenase, MT1-MMP [membrane-type 1 MMP (matrix metalloproteinase); also known as MMP-14]. Furthermore, a cytokine known to mediate fibrosis in vivo, TGF-β1 (transforming growth factor-β1), is up-regulated in human PDAC tumours and can promote MT1-MMP expression. In the present review, we examine the regulation of PDAC progression through the interplay between type I collagen (the most common extracellular matrix present in human PDAC tumours), MT1-MMP and TGF-β1. Specifically, we examine the way in which signalling events through these pathways mediates invasion, regulates microRNAs and contributes to chemoresistance.
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January 2012
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Review Article|
December 21 2011
Biochemical role of the collagen-rich tumour microenvironment in pancreatic cancer progression
Mario A. Shields;
Mario A. Shields
*Division of Hematology/Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, U.S.A.
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Surabhi Dangi-Garimella;
Surabhi Dangi-Garimella
1
*Division of Hematology/Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, U.S.A.
1Correspondence may be addressed to either of these authors (email s-dangi-garimella@northwestern.edu or h-munshi@northwestern.edu).
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Amanda J. Redig;
Amanda J. Redig
†Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, U.S.A.
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Hidayatullah G. Munshi
Hidayatullah G. Munshi
1
*Division of Hematology/Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, U.S.A.
‡The Jesse Brown VA Medical Center, Northwestern University, Chicago, IL 60611, U.S.A.
§The Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, U.S.A.
1Correspondence may be addressed to either of these authors (email s-dangi-garimella@northwestern.edu or h-munshi@northwestern.edu).
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Publisher: Portland Press Ltd
Received:
July 11 2011
Revision Received:
August 30 2011
Accepted:
September 05 2011
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biochem J (2012) 441 (2): 541–552.
Article history
Received:
July 11 2011
Revision Received:
August 30 2011
Accepted:
September 05 2011
Citation
Mario A. Shields, Surabhi Dangi-Garimella, Amanda J. Redig, Hidayatullah G. Munshi; Biochemical role of the collagen-rich tumour microenvironment in pancreatic cancer progression. Biochem J 15 January 2012; 441 (2): 541–552. doi: https://doi.org/10.1042/BJ20111240
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