Tissue-Specific Human Extracellular Matrix Scaffolds Promote Pancreatic Tumour Progression and Chemotherapy Resistance

被引:6
|
作者
Al-Akkad, Walid [1 ,2 ]
Acedo, Pilar [1 ]
Vilia, Maria-Giovanna [1 ,2 ]
Frenguelli, Luca [1 ,2 ]
Ney, Alexander [1 ]
Rodriguez-Hernandez, Irene [2 ]
Labib, Peter L. [1 ]
Tamburrino, Domenico [3 ]
Spoletini, Gabriele [3 ]
Hall, Andrew R. [1 ,4 ]
Canestrari, Simone [1 ]
Osnato, Anna [5 ,6 ]
Garcia-Bernardo, Jose [6 ]
Sejour, Leinal [7 ,8 ]
Vassileva, Vessela [9 ]
Vlachos, Ioannis S. [7 ,8 ]
Fusai, Giuseppe [3 ]
Luong, Tu Vinh [1 ,4 ]
Whittaker, Steven R. [2 ]
Pereira, Stephen P. [1 ]
Vallier, Ludovic [5 ,6 ]
Pinzani, Massimo [1 ]
Rombouts, Krista [1 ]
Mazza, Giuseppe [1 ,2 ]
机构
[1] UCL, Royal Free Hosp, UCL Inst Liver & Digest Hlth, London NW3 2PF, England
[2] Engitix Therapeut, 195 Wood Lane, London W12 7FQ, England
[3] UCL, Royal Free London NHS Fdn Trust, Div Surg, London NW3 2QG, England
[4] Royal Free London NHS Fdn Trust, Sheila Sherlock Liver Ctr, London NW3 2PF, England
[5] Univ Cambridge, Wellcome Trust MRC Cambridge Stem Cell Inst, Anne McLaren Lab, Cambridge CB2 0AW, England
[6] Wellcome Trust Sanger Inst, Hinxton CB10 1RQ, Cambs, England
[7] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Canc Res Inst, Dept Pathol,HMS Initiat RNA Med, Boston, MA 02115 USA
[8] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA
[9] Imperial Coll London, Dept Surg & Canc, London SW7 2AZ, England
关键词
tissue engineering; 3D cell-culture; tissue-specificity; extracellular matrix; pancreatic ductal adenocarcinoma; liver metastasis; chemoresistance; STROMA INTERACTIONS; CANCER; CELL; CARCINOMA; HEDGEHOG; PATHWAY;
D O I
10.3390/cells11223652
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Over 80% of patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed at a late stage and are locally advanced or with concurrent metastases. The aggressive phenotype and relative chemo- and radiotherapeutic resistance of PDAC is thought to be mediated largely by its prominent stroma, which is supported by an extracellular matrix (ECM). Therefore, we investigated the impact of tissue-matched human ECM in driving PDAC and the role of the ECM in promoting chemotherapy resistance. Decellularized human pancreata and livers were recellularized with PANC-1 and MIA PaCa-2 (PDAC cell lines), as well as PK-1 cells (liver-derived metastatic PDAC cell line). PANC-1 cells migrated into the pancreatic scaffolds, MIA PaCa-2 cells were able to migrate into both scaffolds, whereas PK-1 cells were able to migrate into the liver scaffolds only. These differences were supported by significant deregulations in gene and protein expression between the pancreas scaffolds, liver scaffolds, and 2D culture. Moreover, these cell lines were significantly more resistant to gemcitabine and doxorubicin chemotherapy treatments in the 3D models compared to 2D cultures, even after confirmed uptake by confocal microscopy. These results suggest that tissue-specific ECM provides the preserved native cues for primary and metastatic PDAC cells necessary for a more reliable in vitro cell culture.
引用
收藏
页数:23
相关论文
共 50 条
  • [1] Tissue-specific extracellular matrix scaffolds for the regeneration of spatially complex musculoskeletal tissues
    Cunniffe, Grainne M.
    Diaz-Payno, Pedro J.
    Sheehy, Eamon J.
    Critchley, Susan E.
    Almeida, Henrique V.
    Pitacco, Pierluca
    Carroll, Simon F.
    Mahon, Olwyn R.
    Dunne, Aisling
    Levingstone, Tanya J.
    Moran, Conor J.
    Brady, Robert T.
    O'Brien, Fergal J.
    Brama, Pieter A. J.
    Kelly, Daniel J.
    BIOMATERIALS, 2019, 188 : 63 - 73
  • [2] TISSUE-SPECIFIC EXTRACELLULAR-MATRIX COMPONENTS
    LEIVO, I
    PATHOLOGY RESEARCH AND PRACTICE, 1987, 182 (04) : 518 - 518
  • [3] Tissue-Specific Effects of Esophageal Extracellular Matrix
    Keane, Timothy J.
    DeWard, Aaron
    Londono, Ricardo
    Saldin, Lindsey T.
    Castleton, Arthur A.
    Carey, Lisa
    Nieponice, Alejandro
    Lagasse, Eric
    Badylak, Stephen F.
    TISSUE ENGINEERING PART A, 2015, 21 (17-18) : 2293 - 2300
  • [4] BIPHASIC TISSUE-SPECIFIC EXTRACELLULAR MATRIX DERIVED SCAFFOLDS PROMOTE ZONALLY DEFINED ARTICULAR CARTILAGE REGENERATION IN A CAPRINE OSTEOCHONDRAL DEFECT MODEL
    Browe, David
    Payno, Pedro Diaz
    Schipani, Rossana
    Freeman, Fiona
    Burdis, Ross
    Ahern, Daniel
    Randell, Lindsey
    Guler, Selcan
    Nulty, Jessica
    Buckey, Conor
    Brama, Pieter
    Kelly, Daniel
    TISSUE ENGINEERING PART A, 2022, 28 : S494 - S494
  • [5] Electrospun scaffold tailored for tissue-specific extracellular matrix
    Nanoscience and Nanotechnology Initiative, National University of Singapore, Singapore
    不详
    不详
    不详
    Biotechnol. J., 2006, 9 (918-929):
  • [6] Thermoresponsive, Photocrosslinkable and Tissue-Specific Extracellular Matrix Hydrogels
    Coluccino, L.
    Rothrauff, B.
    Gottardi, R.
    Alexander, P.
    Tuan, R. S.
    Diaspro, A.
    Scaglione, S.
    Ceseracciu, L.
    TISSUE ENGINEERING PART A, 2015, 21 : S255 - S255
  • [7] Processing Tissue-Specific Extracellular Matrix for Use as Electrospun Meshes
    Smoak, M.
    Kishan, A.
    Cosgriff-Hernandez, E.
    Mikos, A.
    TISSUE ENGINEERING PART A, 2017, 23 : S68 - S68
  • [8] Complex extracellular matrices promote tissue-specific stem cell differentiation
    Philip, D
    Chen, SS
    Fitzgerald, W
    Orenstein, J
    Margolis, L
    Kleinman, HK
    STEM CELLS, 2005, 23 (02) : 288 - 296
  • [9] Spatial Presentation of Tissue-Specific Extracellular Matrix Components along Electrospun Scaffolds for Tissue Engineering the Bone-Ligament Interface
    Olvera, Dinorath
    Sathy, Binulal N.
    Kelly, Daniel J.
    ACS BIOMATERIALS SCIENCE & ENGINEERING, 2020, 6 (09) : 5145 - 5161
  • [10] IDENTIFICATION OF A HUMAN PANCREATIC DUCT TISSUE-SPECIFIC ANTIGEN
    GOLD, DV
    HOLLINGSWORTH, P
    KREMER, T
    NELSON, D
    CANCER RESEARCH, 1983, 43 (01) : 235 - 238