title: Senescent stroma promotes prostate cancer progression: the role of miR-210.
abstract: We focused our interest on senescent human-derived fibroblasts in the progression of prostate cancer. Hypoxic senescent fibroblasts promote prostate cancer aggressiveness by inducing epithelial to mesenchymal transition (EMT) and by secreting energy-rich compounds to support cancer cell growth. Hypoxic senescent fibroblasts additionally increase: i) the recruitment of monocytes and their M2-macrophage polarization, ii) the recruitment of bone marrow-derived endothelial precursor cells, facilitating their vasculogenic ability and iii) capillary morphogenesis, proliferation and invasion of human mature endothelial cells. In addition, we highlight that overexpression of the hypoxia-induced miR-210 in young fibroblasts increases their senescence-associated features and converts them into cancer associated fibroblast (CAF)-like cells, able to promote cancer cells EMT, to support angiogenesis and to recruit endothelial precursor cells and monocytes/macrophages.
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy. Electronic address: marialetizia.taddei@unifi.it.
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Taddei
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Cavallini
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Comito
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Giannoni
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Amadeo 42, 20133 Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Folini
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B 07100 Sassari, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Marini
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Amadeo 42, 20133 Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Gandellini
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Morandi
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B 07100 Sassari, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Pintus
authors.affiliation: Histology and Molecular Diagnostic, University Hospital Careggi, Viale G.B. Morgagni 85, 50134 Florence, Italy.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Raspollini
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Amadeo 42, 20133 Milan, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Zaffaroni
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy; Center for Research, Transfer and High Education 'Study at Molecular and Clinical Level of Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development on Novel Therapies', Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Chiarugi
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: C543800:MIRN210 microRNA, human; D035683:MicroRNAs
keywords: Prostate cancer; Senescence; Tumor microenvironment; miR-210
references.citation: Mol Cell Biol. 1996 Sep;16(9):5210-8
references.pmid: 8756678
references.citation: Mol Oncol. 2014 Dec;8(8):1729-46
references.pmid: 25091736
references.citation: Antioxid Redox Signal. 2012 Jun 1;16(11):1248-63
references.pmid: 21929373
references.citation: Clin Cancer Res. 2000 Jul;6(7):2702-6
references.pmid: 10914713
references.citation: PLoS One. 2010 Nov 16;5(11):e14003
references.pmid: 21103368
references.citation: Nature. 2000 Nov 9;408(6809):248-54
references.pmid: 11089982
references.citation: J Mol Med (Berl). 2013 Jan;91(1):103-15
references.pmid: 22903544
references.citation: Mech Ageing Dev. 2005 Jan;126(1):59-69
references.pmid: 15610763
references.citation: Cancer Microenviron. 2012 Apr;5(1):39-44
references.pmid: 21706180
references.citation: J Cell Sci. 2005 Feb 1;118(Pt 3):485-96
references.pmid: 15657080
references.citation: Oncogene. 2014 May 8;33(19):2423-31
references.pmid: 23728338
references.citation: Genes Dev. 1994 Nov 1;8(21):2540-51
references.pmid: 7958916
references.citation: Annu Rev Pathol. 2010;5:99-118
references.pmid: 20078217
references.citation: Exp Dermatol. 2011 Oct;20(10):836-8
references.pmid: 21707762
references.citation: Cell. 2011 Mar 4;144(5):646-74
references.pmid: 21376230
references.citation: Cell. 2005 May 6;121(3):335-48
references.pmid: 15882617
references.citation: Cell. 1997 Mar 7;88(5):593-602
references.pmid: 9054499
references.citation: Cancer Res. 2006 Jan 15;66(2):794-802
references.pmid: 16424011
references.citation: Int J Biochem Cell Biol. 2002 Nov;34(11):1401-14
references.pmid: 12200035
references.citation: Thorax. 2010 Aug;65(8):733-8
references.pmid: 20685750
references.citation: Nat Protoc. 2010 Sep;5(9):1596-607
references.pmid: 21085125
references.citation: Cancer Cell. 2010 Feb 17;17(2):135-47
references.pmid: 20138012
references.citation: Proc Natl Acad Sci U S A. 1995 May 9;92(10):4337-41
references.pmid: 7753808
references.citation: Nat Rev Cancer. 2006 May;6(5):392-401
references.pmid: 16572188
references.citation: Oncogene. 1998 Mar 5;16(9):1113-23
references.pmid: 9528853
references.citation: Biochem Biophys Res Commun. 2013 Aug 2;437(3):397-402
references.pmid: 23831470
references.citation: Semin Cancer Biol. 2011 Dec;21(6):354-9
references.pmid: 21925603
references.citation: Cancer Res. 2010 Sep 1;70(17):6945-56
references.pmid: 20699369
references.citation: Nat Rev Cancer. 2002 Jan;2(1):38-47
references.pmid: 11902584
references.citation: Blood. 2011 Sep 29;118(13):3743-55
references.pmid: 21803847
references.citation: Biol Pharm Bull. 2011;34(7):1072-7
references.pmid: 21720015
references.citation: Nucleic Acids Res. 2014 Feb;42(3):1606-18
references.pmid: 24217920
references.citation: Oncogene. 2002 Jan 21;21(4):503-11
references.pmid: 11850775
references.citation: Cancer Lett. 2012 Nov 1;324(1):31-41
references.pmid: 22659468
references.citation: Oncogene. 2010 Jul 29;29(30):4362-8
references.pmid: 20498629
references.citation: Nucleic Acids Res. 2002 Jan 15;30(2):545-9
references.pmid: 11788717
references.citation: PLoS Biol. 2008 Dec 2;6(12):2853-68
references.pmid: 19053174
references.citation: EMBO Mol Med. 2010 Jun;2(6):211-30
references.pmid: 20535745
references.citation: Exp Cell Res. 1965 Mar;37:614-36
references.pmid: 14315085
references.citation: Cell Death Differ. 2011 Mar;18(3):465-78
references.pmid: 20885442
references.citation: Proc Natl Acad Sci U S A. 2001 Oct 9;98(21):12072-7
references.pmid: 11593017
references.citation: Cancer Res. 2001 Aug 15;61(16):5974-8
references.pmid: 11507037
references.citation: Curr Opin Genet Dev. 2002 Feb;12(1):80-5
references.pmid: 11790559
references.citation: Exp Cell Res. 2010 May 1;316(8):1324-31
references.pmid: 20211171
references.citation: Cell Cycle. 2012 Jun 15;11(12):2285-302
references.pmid: 22684298
references.citation: Cancer Res. 2012 Oct 1;72(19):5130-40
references.pmid: 22850421
references.citation: J Clin Invest. 2013 Mar;123(3):966-72
references.pmid: 23454759
references.citation: J Biol Chem. 2001 Jan 26;276(4):2531-7
references.pmid: 11060295
references.citation: Cancer Metastasis Rev. 2012 Jun;31(1-2):195-208
references.pmid: 22101652
references.citation: Exp Gerontol. 2006 Jul;41(7):674-82
references.pmid: 16713693
references.citation: Cancer Res. 2009 Feb 1;69(3):1221-9
references.pmid: 19141645
references.citation: Proc Natl Acad Sci U S A. 2010 Apr 13;107(15):6976-81
references.pmid: 20308562
references.citation: J Cell Physiol. 1982 Sep;112(3):419-24
references.pmid: 6127343
references.citation: Oncogene. 2011 May 19;30(20):2345-55
references.pmid: 21258401
references.citation: Cell Death Differ. 2012 Apr;19(4):713-21
references.pmid: 22052189
references.citation: J Cell Sci. 2006 Jul 1;119(Pt 13):2727-38
references.pmid: 16757516
references.citation: Antioxid Redox Signal. 2011 Jun 15;14(12):2361-71
references.pmid: 21235356
references.citation: J Biol Chem. 2011 Jan 7;286(1):420-8
references.pmid: 21044961
references.citation: FASEB J. 2005 May;19(7):854-6
references.pmid: 15857893
references.citation: Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16472-7
references.pmid: 17060621