CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan

doi:10.1038/ncomms14383

GSTDTAP > 资源环境科学

DOI	10.1038/ncomms14383
	CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan
	Vennin, Claire 1; 39;Connnor, Chelsie 2; 39;Rourke, Thomas J.3
	2019-08-12
发表期刊	NATURE COMMUNICATIONS
ISSN	2041-1723
出版年	2019
卷号	10
文章类型	Article
语种	英语
国家	Australia; Netherlands; Scotland; USA; New Zealand; Italy
英文摘要	Heterogeneous subtypes of cancer-associated fibroblasts (CAFs) coexist within pancreatic cancer tissues and can both promote and restrain disease progression. Here, we interrogate how cancer cells harboring distinct alterations in p53 manipulate CAFs. We reveal the existence of a p53-driven hierarchy, where cancer cells with a gain-of-function (GOF) mutant p53 educate a dominant population of CAFs that establish a pro-metastatic environment for GOF and null p53 cancer cells alike. We also demonstrate that CAFs educated by null p53 cancer cells may be reprogrammed by either GOF mutant p53 cells or their CAFs. We identify perlecan as a key component of this pro-metastatic environment. Using intravital imaging, we observe that these dominant CAFs delay cancer cell response to chemotherapy. Lastly, we reveal that depleting perlecan in the stroma combined with chemotherapy prolongs mouse survival, supporting it as a potential target for anti-stromal therapies in pancreatic cancer.
领域	资源环境
收录类别	SCI-E
WOS记录号	WOS:000480385800007
WOS关键词	MUTANT P53 ; DUCTAL ADENOCARCINOMA ; MUTATIONAL LANDSCAPE ; MOUSE MODELS ; TUMOR-CELLS ; FIBROBLASTS ; ACTIVATION ; INVASION ; STROMA ; IMMUNOTHERAPY
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
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引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/203218
专题	资源环境科学
作者单位	1.Garvan Inst Med Res, Sydney, NSW 2010, Australia; 2.Kinghorn Canc Ctr, Sydney, NSW 2010, Australia; 3.Univ New South Wales Sydney, Fac Med, St Vincents Clin Sch, Sydney, NSW 2010, Australia; 4.Netherlands Canc Inst, Mol Pathol Dept, NL-1066 CX Amsterdam, Netherlands; 5.Univ New South Wales Sydney, Grad Sch Biomed Engn, Sydney, NSW 2052, Australia; 6.Canc Res UK Beatson Inst, Glasgow G61 BD, Lanark, Scotland; 7.La Trobe Univ, Sch Life Sci, Dept Physiol Anat & Microbiol, Bundoora, Vic, Australia; 8.Cornell Univ, Coll Vet Med, Dept Biomed Sci, Ithaca, NY 14853 USA; 9.Univ Calif San Diego, Inst Engn Med, Dept Bioengn, San Diego, CA 92121 USA; 10.Univ Sydney, Childrens Med Res Inst, Sydney, NSW 2006, Australia; 11.Univ Otago, Dunedin Sch Med, Dept Pathol, Dunedin 9054, New Zealand; 12.Univ Otago, Maurice Wilkins Ctr, Dunedin 9054, New Zealand; 13.Univ New South Wales, Lowy Canc Res Ctr, Biomed Imaging Facil, Sydney, NSW, Australia; 14.Univ New South Wales, Lowy Canc Res Ctr, Sch Med Sci, Pancreat Canc Translat Res Grp, Sydney, NSW 2052, Australia; 15.Univ New South Wales, Australian Ctr Nanomed, Sydney, NSW 2052, Australia; 16.Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia; 17.Royal North Shore Hosp, Dept Anat Pathol, NSW Hlth Pathol, Sydney, NSW 2065, Australia; 18.Kolling Inst Med Res, Canc Diag & Pathol Res Grp, St Leonards, NSW 2065, Australia; 19.Univ Sydney, Sch Life & Environm Sci, Charles Perkin Ctr, Sydney, NSW 2006, Australia; 20.Garvan Inst Med Res, Kinghorn Canc Ctr, 370 Victoria St, Sydney, NSW 2010, Australia; 21.Wollongong Hosp Illawarra & Shoalhaven Local Hlth, Loftus St, Wollongong, NSW 2500, Australia; 22.Royal North Shore Hosp, Westbourne St, St Leonards, NSW 2065, Australia; 23.QIMR Berghofer Med Res Inst, 300 Herston Rd, Herston, Qld 4006, Australia; 24.Univ Melbourne, Ctr Canc Res, Victorian Comprehens Canc Ctr, 305 Grattan St, Melbourne, Vic 3000, Australia; 25.Univ Qld, Inst Mol Biosci, St Lucia, Qld 4072, Australia; 26.Bankstown Hosp, Eldridge Rd, Bankstown, NSW 2200, Australia; 27.Liverpool Hosp, Elizabeth St, Liverpool, NSW 2170, Australia; 28.St Vincents Hosp, 390 Victoria St, Darlinghurst, NSW 2010, Australia; 29.Westmead Hosp, Hawkesbury & Darcy Rd, Westmead, NSW 2145, Australia; 30.Royal Prince Alfred Hosp, Missenden Rd, Camperdown, NSW 2050, Australia; 31.Prince Wales Hosp, Barker St, Randwick, NSW 2031, Australia; 32.Fremantle Hosp, Alma St, Fremantle, WA 6959, Australia; 33.Sir Charles Gairdner Hosp, Hosp Ave, Nedlands, WA 6009, Australia; 34.St John God Healthcare, 12 Salvado Rd, Subiaco, WA, Australia; 35.Royal Adelaide Hosp, Adelaide, SA 5000, Australia; 36.Flinders Med Ctr, Flinders Dr, Bedford Pk, SA 5042, Australia; 37.Envoi Pathol, 1-49 Butterfield St, Herston, Qld 4006, Australia; 38.Princess Alexandria Hosp, Cornwall St & Ipswich Rd, Woolloongabba, Qld 4102, Australia; 39.Austin Hosp, 145 Studley Rd, Heidelberg, Vic 3084, Australia; 40.Johns Hopkins Med Inst, 600 North Wolfe St, Baltimore, MD 21287 USA; 41.Univ Verona, Arc Net Ctr Appl Res Canc, Via Artigliere, I-37129 Verona, Italy; 42.Univ Glasgow, Inst Canc Sci, Wolfson Wohl Canc Res Ctr, Switchback Rd, Glasgow G61 1BD, Lanark, Scotland
推荐引用方式 GB/T 7714	Vennin, Claire,39;Connnor, Chelsie,39;Rourke, Thomas J.. CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan[J]. NATURE COMMUNICATIONS,2019,10.
APA	Vennin, Claire,39;Connnor, Chelsie,&39;Rourke, Thomas J..(2019).CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan.NATURE COMMUNICATIONS,10.
MLA	Vennin, Claire,et al."CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan".NATURE COMMUNICATIONS 10(2019).