title: Understanding tumor heterogeneity as functional compartments--superorganisms revisited.
abstract: Compelling evidence broadens our understanding of tumors as highly heterogeneous populations derived from one common progenitor. In this review we portray various stages of tumorigenesis, tumor progression, self-seeding and metastasis in analogy to the superorganisms of insect societies to exemplify the highly complex architecture of a neoplasm as a system of functional "castes."Accordingly, we propose a model in which clonal expansion and cumulative acquisition of genetic alterations produce tumor compartments each equipped with distinct traits and thus distinct functions that cooperate to establish clinically apparent tumors. This functional compartment model also suggests mechanisms for the self-construction of tumor stem cell niches. Thus, thinking of a tumor as a superorganism will provide systemic insight into its functional compartmentalization and may even have clinical implications.
authors: Department of Pediatrics, Klinikum rechts der Isar, Technische Universität München, Kölner Platz 1, Munich, Germany. thomas.gruenewald@lrz.tum.de
authors: Thomas G P
authors: TG
authors: Grunewald
authors: Saskia M
authors: SM
authors: Herbst
authors: Jürgen
authors: J
authors: Heinze
authors: Stefan
authors: S
authors: Burdach
references: Prog Exp Tumor Res. 1970;13:1-27
references: 4921480
references: Nat Immunol. 2002 Nov;3(11):991-8
references: 12407406
references: Nat Rev Cancer. 2002 Oct;2(10):795-803
references: 12360282
references: Cancer Cell. 2009 Jun 2;15(6):539-50
references: 19477432
references: J Theor Biol. 1964 Jul;7(1):17-52
references: 5875340
references: Trends Ecol Evol. 2005 Oct;20(10):545-52
references: 16701433
references: Cell. 2000 Oct 13;103(2):295-309
references: 11057902
references: Mol Oncol. 2010 Jun;4(3):267-83
references: 20537601
references: Crit Rev Oncog. 2009;15(1-2):65-90
references: 20136628
references: Philos Trans R Soc Lond B Biol Sci. 2009 Nov 12;364(1533):3143-55
references: 19805423
references: Dev Cell. 2010 Jun 15;18(6):884-901
references: 20627072
references: Br Foreign Med Chir Rev. 1860 Apr;25(50):367-404
references: 30164232
references: Cancer Metastasis Rev. 2009 Jun;28(1-2):113-27
references: 19153673
references: Nat Rev Cancer. 2007 Nov;7(11):834-46
references: 17957189
references: Science. 1988 Jul 1;241(4861):58-62
references: 2898810
references: Cancer Res. 2002 Dec 1;62(23):6791-5
references: 12460886
references: Cell. 2008 May 16;133(4):704-15
references: 18485877
references: Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2233-8
references: 10051624
references: Cell Stem Cell. 2007 Dec 13;1(6):607-11
references: 18371402
references: Nat Immunol. 2002 Nov;3(11):999-1005
references: 12407407
references: Science. 2005 Apr 8;308(5719):264-7
references: 15821094
references: Nature. 2006 Jan 5;439(7072):76-8
references: 16397498
references: Nat Rev Cancer. 2006 Dec;6(12):924-35
references: 17109012
references: Science. 2003 Sep 26;301(5641):1867-70
references: 14512616
references: Neoplasia. 2008 Nov;10(11):1170-82
references: 18953426
references: Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5324-9
references: 19289832
references: Nat Rev Cancer. 2009 Apr;9(4):302-12
references: 19308069
references: Oncogene. 2004 Sep 20;23(43):7274-82
references: 15378087
references: Bioessays. 2004 Mar;26(3):291-9
references: 14988930
references: Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8
references: 12629218
references: Front Zool. 2009 Oct 28;6:27
references: 19863794
references: J Clin Oncol. 2008 Jun 10;26(17):2839-45
references: 18539962
references: Bioessays. 2009 Feb;31(2):190-7
references: 19204991
references: Proc Natl Acad Sci U S A. 2000 May 23;97(11):5948-53
references: 10811892
references: Cancer Res. 2001 Apr 1;61(7):2929-34
references: 11306470
references: Nat Rev Cancer. 2008 Feb;8(2):141-7
references: 18185517
references: Am J Pathol. 2000 Feb;156(2):383-8
references: 10666365
references: Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6075-9
references: 11959924
references: Nat Rev Cancer. 2007 Apr;7(4):246-55
references: 17384580
references: Q Rev Biol. 2010 Mar;85(1):57-79
references: 20337260
references: Cell. 2009 Dec 24;139(7):1315-26
references: 20064377
references: Science. 2002 Dec 20;298(5602):2345-9
references: 12493905
references: Int J Dev Biol. 2004;48(5-6):441-9
references: 15349818
references: APMIS. 2004 Jul-Aug;112(7-8):508-25
references: 15563313
references: Eur J Endocrinol. 2010 Apr;162(4):813-8
references: 20133447
references: Nature. 2004 Nov 18;432(7015):396-401
references: 15549107
references: Monogr Popul Biol. 1978;12:1-352
references: 740003
references: J Clin Invest. 2010 Jan;120(1):41-50
references: 20051635
references: Immunology. 2007 May;121(1):1-14
references: 17386080
references: Nat Rev Cancer. 2009 Apr;9(4):239-52
references: 19279573
references: Nat Rev Cancer. 2005 Aug;5(8):591-602
references: 16056258
references: J Surg Oncol. 2011 Apr;103(5):380-5
references: 21400519
references: Crit Rev Oncol Hematol. 2004 Jul;51(1):1-28
references: 15207251
references: Nat Med. 2009 Jul;15(7):750-6
references: 19584866
references: Nature. 2006 Jun 29;441(7097):1068-74
references: 16810241
references: Nat Rev Cancer. 2008 Oct;8(10):755-68
references: 18784658
references: Nat Rev Cancer. 2005 Aug;5(8):649-55
references: 16056260
references: J Clin Oncol. 2003 Aug 15;21(16):3072-8
references: 12915596
references: Ann Oncol. 2010 Aug;21(8):1733-1734
references: 20605931
references: Cancer Metastasis Rev. 2008 Mar;27(1):5-10
references: 18066649
references: Theor Biol Med Model. 2010 Nov 09;7:42
references: 21062473
references: Clin Cancer Res. 2010 Aug 15;16(16):4256-67
references: 20610556
references: Adv Cancer Res. 2003;89:35-67
references: 14587870
references: Curr Cancer Drug Targets. 2009 Dec;9(8):963-81
references: 20025605
references: Adv Cancer Res. 1998;72:25-56
references: 9338073
references: Clin Cancer Res. 2006 Jan 15;12(2):332-9
references: 16428469
references: Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14800-3
references: 8962135
references: Nat Rev Cancer. 2004 Mar;4(3):227-35
references: 14993904
references: Cancer Res. 2004 Nov 15;64(22):8213-21
references: 15548687
references: Nature. 1994 Feb 17;367(6464):645-8
references: 7509044
references: Stem Cells. 2009 Jan;27(1):18-28
references: 19224508
references: Nat Rev Genet. 2008 Oct;9(10):735-48
references: 18802413
references: Nature. 2001 Nov 1;414(6859):105-11
references: 11689955
references: Cell. 2010 Jul 23;142(2):218-29
references: 20655465
references: Nat Med. 2010 Jan;16(1):98-105
references: 20037595
references: Cancer Res. 2010 Oct 15;70(20):8003-14
references: 20924110
references: J Mammary Gland Biol Neoplasia. 2010 Jun;15(2):191-9
references: 20369376
references: Cell. 2009 Sep 4;138(5):822-9
references: 19737509
references: Nature. 2007 Jan 4;445(7123):106-10
references: 17122772
references: Annu Rev Med. 1979;30:135-43
references: 400484
references: J Theor Biol. 1964 Jul;7(1):1-16
references: 5875341
references: Br J Cancer. 2010 May 25;102(11):1645-53
references: 20461080