title: Biochemical role of the collagen-rich tumour microenvironment in pancreatic cancer progression.
abstract: 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.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Mario A
authors.initials: MA
authors.lastname: Shields
authors.forename: Surabhi
authors.initials: S
authors.lastname: Dangi-Garimella
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Redig
authors.forename: Hidayatullah G
authors.initials: HG
authors.lastname: Munshi
mesh_terms: D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology; D024042:Collagen Type I / Q000378:metabolism*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D005355:Fibrosis; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000502:physiology; D035683:MicroRNAs / Q000378:metabolism; D058628:Myofibroblasts / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: D024042:Collagen Type I; D035683:MicroRNAs; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D053511:Matrix Metalloproteinase 14