title: Adult adipose-derived stem cells and breast cancer: a controversial relationship.
abstract: Breast cancer is the most common cancer in women and autologous fat grafting is an important clinical application in treatment of post-surgical deformities. The simplicity of fat grafting procedures and the absence of subsequent visible scar prompted an increasing interest for this technique. The plasticity of adipose-derived stem cells (ASCs) obtained from stromal vascular fraction (SVF) of adult adipose tissue provided exciting perspectives for regenerative medicine and surgery. The recent discovery that SVF/ASC enrichment further ameliorates clinical efficacy of grafting ASCs suggest as ASC-mediated new adipogenesis and vasculogenesis. ASC adipogenic differentiation involves Akt activity and EGFRs, FGFRs, ERbB2 receptor-mediated pathways that also play a pivotal role in the regulation of breast cancer growth. Moreover, the finding that platelet-derived growth factors and hormones improved long-term maintenance of fat grafting raises new concerns for their use during breast reconstruction after cancer surgery. However, it remains unclear whether grafted or resident ASCs may increase the risk of de novo cancer development or recurrence. Preliminary follow-up studies seem to support the efficacy and safety of SVF/ASCs enrichment and the additional benefit from the combined use of autologous platelet-derived growth factors and hormones during breast reconstruction procedures. In the present review we highlighted the complex interplay between resident or grafted ASCs, mature adipocytes, dormant or active breast cancer cells and tumor microenvironment. Actually, data concerning the permissive role of ASCs on breast cancer progression are contrasting, although no clear evidence speaking against their use exists.
authors.affiliation: Anatomic Pathology, Tor Vergata University of Rome, Via Montpellier, 00133 Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bielli
authors.affiliation: Anatomic Pathology, Tor Vergata University of Rome, Via Montpellier, 00133 Rome, Italy.
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Scioli
authors.affiliation: Plastic Surgery, Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Gentile
authors.affiliation: Anatomic Pathology, Tor Vergata University of Rome, Via Montpellier, 00133 Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Agostinelli
authors.affiliation: Anatomic Pathology, Tor Vergata University of Rome, Via Montpellier, 00133 Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Tarquini
authors.affiliation: Plastic Surgery, Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Cervelli
authors.affiliation: Anatomic Pathology, Tor Vergata University of Rome, Via Montpellier, 00133 Rome, Italy.
authors.forename: Augusto
authors.initials: A
authors.lastname: Orlandi
keywords: Adipose-derived stem cell; Akt; Breast cancer; Breast reconstruction; Carcinogenesis; Fat grafting; Stromal vascular fraction
references.citation: Stem Cells Transl Med. 2012 Mar;1(3):206-20
references.pmid: 23197780
references.citation: Surg Innov. 2013 Aug;20(4):370-6
references.pmid: 22964262
references.citation: Tissue Eng. 2001 Apr;7(2):211-28
references.pmid: 11304456
references.citation: Tissue Eng Part C Methods. 2009 Dec;15(4):625-34
references.pmid: 19231923
references.citation: J Natl Cancer Inst. 2004 Nov 3;96(21):1593-603
references.pmid: 15523088
references.citation: Atherosclerosis. 2012 Sep;224(1):51-7
references.pmid: 22857896
references.citation: J Pathol. 2003 Oct;201(2):221-8
references.pmid: 14517839
references.citation: Cytometry A. 2013 Jan;83(1):5-7
references.pmid: 23081699
references.citation: Cancer Lett. 2009 Oct 18;284(1):80-5
references.pmid: 19427114
references.citation: Front Oncol. 2013 Sep 23;3:250
references.pmid: 24069582
references.citation: Clin Chem. 2009 Aug;55(8):1453-5
references.pmid: 19541862
references.citation: Plast Reconstr Surg. 2009 Jul;124(1):272-280
references.pmid: 19346997
references.citation: Curr Pathobiol Rep. 2014 Mar 1;2(1):41-52
references.pmid: 24660130
references.citation: Stem Cells Dev. 2008 Aug;17(4):761-73
references.pmid: 18393634
references.citation: Arterioscler Thromb. 1994 Jun;14(6):982-9
references.pmid: 8199190
references.citation: Biochem Pharmacol. 2012 Jul 15;84(2):163-71
references.pmid: 22525722
references.citation: Cell. 2005 May 6;121(3):335-48
references.pmid: 15882617
references.citation: BMC Cancer. 2013 Nov 09;13:535
references.pmid: 24209831
references.citation: Biochim Biophys Acta. 2012 Aug;1826(1):209-14
references.pmid: 22546620
references.citation: Int J Cancer. 2008 Nov 15;123(10):2229-38
references.pmid: 18777559
references.citation: Cancer Lett. 2012 Nov 28;324(2):142-51
references.pmid: 22643115
references.citation: Breast Cancer Res Treat. 1998;49 Suppl 1:S27-32; discussion S33-7
references.pmid: 9797015
references.citation: Cytotherapy. 2009;11(3):289-98, 1 p following 298
references.pmid: 19308770
references.citation: J Biomed Res. 2012 Sep;26(5):325-35
references.pmid: 23554768
references.citation: Stem Cell Res. 2011 Mar;6(2):103-11
references.pmid: 21195687
references.citation: PLoS One. 2012;7(9):e45877
references.pmid: 23029290
references.citation: Tissue Eng Part A. 2011 Jan;17(1-2):93-106
references.pmid: 20673000
references.citation: Tissue Eng Part A. 2010 Sep;16(9):2953-66
references.pmid: 20486792
references.citation: Science. 2002 May 10;296(5570):1046-9
references.pmid: 12004111
references.citation: Stem Cells Dev. 2013 Dec 1;22(23):3114-27
references.pmid: 23895436
references.citation: PLoS One. 2013 Aug 22;8(8):e74618
references.pmid: 23991224
references.citation: Cancer Sci. 2010 Oct;101(10):2286-92
references.pmid: 20682005
references.citation: Circ Res. 2007 May 11;100(9):1249-60
references.pmid: 17495232
references.citation: Cancer Res. 2010 May 1;70(9):3718-29
references.pmid: 20388793
references.citation: Stem Cells. 2006 Feb;24(2):376-85
references.pmid: 16322640
references.citation: Biochem Pharmacol. 2010 Jun 15;79(12):1706-13
references.pmid: 20117099
references.citation: Tissue Eng Part B Rev. 2010 Dec;16(6):567-75
references.pmid: 20726819
references.citation: Aesthet Surg J. 2009 Sep-Oct;29(5):360-76
references.pmid: 19825464
references.citation: J Gene Med. 2008 Oct;10(10):1071-82
references.pmid: 18671316
references.citation: Stem Cells. 2007 Dec;25(12):3101-10
references.pmid: 17823241
references.citation: Nature. 2007 Oct 4;449(7162):557-63
references.pmid: 17914389
references.citation: EMBO J. 2007 Mar 7;26(5):1268-78
references.pmid: 17304214
references.citation: Mol Carcinog. 2010 Nov;49(11):923-7
references.pmid: 20842668
references.citation: Breast Cancer Res. 2013 Dec 19;15(6):R119
references.pmid: 24355041
references.citation: J Cell Physiol. 2007 Sep;212(3):702-9
references.pmid: 17477371
references.citation: Stem Cells Transl Med. 2012 Apr;1(4):341-51
references.pmid: 23197813
references.citation: Endocr Relat Cancer. 2005 Dec;12(4):721-47
references.pmid: 16322319
references.citation: Cell Stem Cell. 2008 Sep 11;3(3):301-13
references.pmid: 18786417
references.citation: J Plast Reconstr Aesthet Surg. 2011 Apr;64(4):477-83
references.pmid: 20692216
references.citation: PLoS One. 2014 Jan 03;9(1):e84969
references.pmid: 24404198
references.citation: Cell Commun Signal. 2012 Sep 03;10(1):26
references.pmid: 22943670
references.citation: Science. 1999 Apr 2;284(5411):143-7
references.pmid: 10102814
references.citation: J Gene Med. 2012 Dec;14(12):776-87
references.pmid: 23150190
references.citation: Cancer Res. 2011 Apr 1;71(7):2455-65
references.pmid: 21459803
references.citation: Stem Cell Res. 2012 Mar;8(2):247-58
references.pmid: 22265744
references.citation: Br J Cancer. 2013 Oct 15;109(8):2248-58
references.pmid: 24045665
references.citation: Exp Cell Res. 2010 Aug 1;316(13):2087-98
references.pmid: 20420826
references.citation: Proc Natl Acad Sci U S A. 2012 Jun 19;109(25):9786-91
references.pmid: 22665775
references.citation: Mol Cancer Res. 2012 Nov;10(11):1403-18
references.pmid: 23024188
references.citation: J Cell Biochem. 2006 Dec 1;99(5):1285-97
references.pmid: 16795045
references.citation: Curr Stem Cell Res Ther. 2010 Jun;5(2):103-10
references.pmid: 19941460
references.citation: Lancet. 2013 Sep 28;382(9898):1113-20
references.pmid: 24075051
references.citation: Circ Res. 2008 Jan 4;102(1):77-85
references.pmid: 17967785
references.citation: Int J Obes (Lond). 2011 Sep;35(9):1141-53
references.pmid: 21266947
references.citation: Aesthetic Plast Surg. 2010 Aug;34(4):475-80
references.pmid: 20333521
references.citation: Cancer Res. 2010 Mar 1;70(5):1804-13
references.pmid: 20145150
references.citation: Am J Physiol Endocrinol Metab. 2004 Apr;286(4):E577-88
references.pmid: 14600072
references.citation: Cancer Res. 2000 Mar 15;60(6):1604-8
references.pmid: 10749129
references.citation: Mol Cancer Res. 2009 Nov;7(11):1882-92
references.pmid: 19861407
references.citation: Oncogene. 2009 Jul 30;28(30):2745-55
references.pmid: 19483720
references.citation: Nat Rev Mol Cell Biol. 2002 May;3(5):349-63
references.pmid: 11988769
references.citation: Plast Reconstr Surg. 2007 Mar;119(3):775-85; discussion 786-7
references.pmid: 17312477
references.citation: Stem Cells Transl Med. 2012 Mar;1(3):230-6
references.pmid: 23197782
references.citation: Cancer Res. 2010 Mar 1;70(5):2085-94
references.pmid: 20179196
references.citation: J Musculoskelet Neuronal Interact. 2003 Jun;3(2):156-61
references.pmid: 15758356
references.citation: Biomaterials. 2010 Aug;31(24):6279-308
references.pmid: 20493521
references.citation: Curr Opin Mol Ther. 2005 Aug;7(4):300-5
references.pmid: 16121695
references.citation: Circ Res. 2004 Mar 19;94(5):678-85
references.pmid: 14739163
references.citation: Cell Metab. 2012 Feb 8;15(2):222-9
references.pmid: 22326223
references.citation: Am J Physiol Endocrinol Metab. 2001 Jun;280(6):E827-47
references.pmid: 11350765
references.citation: Biochem Biophys Res Commun. 2010 Jul 30;398(3):601-5
references.pmid: 20603108
references.citation: Ann Oncol. 2012 Mar;23(3):582-588
references.pmid: 21610155