title: Generation of erythroid cells from fibroblasts and cancer cells in vitro and in vivo.
abstract: Bone marrow is generally considered the main source of erythroid cells. Here we report that a single hypoxia-mimic chemical, CoCl2, can increase the size of fibroblasts and cancer cells and lead to formation of polyploidy giant cells (PGCs) or polyploidy giant cancer cells (PGCCs), activation of stem cell marker expression, increased growth of normal and cancer spheroid, and lead to differentiation of the fibroblasts and epithelial cells toward erythroid lineage expressing hemoglobins both in vitro and in vivo. Immunohistochemical examination demonstrated that these cells are predominantly made of embryonic hemoglobins, with various levels of fetal and adult hemoglobins. Ectopic expression of c-Myc induced the generation of nucleated erythoid cells expressing variable levels of embryonic and fetal hemoglobins. Generation of these erythroid cells can be also observed via histological examination of other cancer cell lines and human tumor samples. These data suggest that normal and solid cancer cells can directly generate erythroid cells to obtain oxygen in response to hypoxia and may explain the ineffectiveness of conventional anti-angiogenic therapies for cancer, which are directed at endothelium-dependent vessels, and offer new targets for intervention.
authors: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Shiwu
authors: S
authors: Zhang
authors: Imelda
authors: I
authors: Mercado-Uribe
authors: Jinsong
authors: J
authors: Liu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation / Q000235:genetics; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D003035:Cobalt / Q000494:pharmacology; D041905:Erythroid Cells / Q000166:cytology* / Q000187:drug effects; D015672:Erythroid Precursor Cells / Q000166:cytology; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D016259:Genes, myc; D006454:Hemoglobins / Q000096:biosynthesis; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D010051:Ovarian Neoplasms / Q000473:pathology*; D010053:Ovary / Q000166:cytology; D018874:Spheroids, Cellular / Q000187:drug effects
chemical_list: D015415:Biomarkers; D006454:Hemoglobins; D003035:Cobalt; C018021:cobaltous chloride
references: Biochem Pharmacol. 2000 Jul 1;60(1):31-40
references: 10807942
references: Blood. 2001 Feb 15;97(4):1099-105
references: 11159543
references: Int J Vasc Med. 2012;2012:918267
references: 22611498
references: Nat Rev Clin Oncol. 2011 May 31;8(7):393-404
references: 21629216
references: Exp Hematol. 2009 Sep;37(9):1007-15
references: 19500646
references: Cancer Res. 2004 Mar 1;64(5):1655-63
references: 14996724
references: Pharmacol Rev. 2004 Dec;56(4):549-80
references: 15602010
references: Science. 2008 Nov 7;322(5903):949-53
references: 18845712
references: Biochim Biophys Acta. 1986 Apr 29;886(2):203-13
references: 3008852
references: J Biol Chem. 1984 Jun 10;259(11):7325-30
references: 6539334
references: N Engl J Med. 1973 Jul 12;289(2):58-62
references: 4710406
references: Bioconjug Chem. 2000 Jan-Feb;11(1):46-50
references: 10639084
references: Blood. 2011 Jan 20;117(3):839-47
references: 21037085
references: Aust N Z J Med. 1975 Aug;5(4):306-14
references: 810127
references: Nature. 1979 Jul 12;280(5718):164-5
references: 95354
references: Cell. 2007 May 4;129(3):465-72
references: 17482542
references: Adv Exp Med Biol. 2002;509:231-49
references: 12572997
references: Nature. 2010 Nov 25;468(7323):521-6
references: 21057492
references: Br J Haematol. 1999 Feb;104(2):258-65
references: 10050705
references: Clin Cancer Res. 2010 Jun 15;16(12):3171-81
references: 20423983
references: Cell. 2006 Aug 25;126(4):663-76
references: 16904174
references: J Clin Oncol. 2011 Feb 10;29(5):591-9
references: 21220598
references: J Cell Biol. 1982 Jun;93(3):828
references: 6889600
references: Cancer Lett. 2007 May 8;249(2):188-97
references: 16997457
references: Cancer Lett. 2007 Sep 8;254(2):157-64
references: 17306454
references: Carcinogenesis. 2007 Jan;28(1):174-82
references: 16829690
references: Blood Rev. 1998 Jun;12(2):106-14
references: 9661799
references: Cell Stem Cell. 2010 Dec 3;7(6):651-5
references: 21112560
references: Blood. 1992 May 1;79(9):2471-4
references: 1571559
references: Nature. 1985 Jan 17-23;313(5999):235-8
references: 2578614
references: Cell Differ. 1984 Jun;14(2):87-97
references: 6205767
references: Nature. 1961 Feb 11;189:496-7
references: 13716547
references: Q J Med. 1976 Apr;45(178):277-94
references: 940922
references: Blood. 2009 Sep 3;114(10):2097-106
references: 19372257
references: Nature. 1975 Mar 27;254(5498):335-7
references: 1118015
references: Immunity. 2001 Jan;14(1):45-55
references: 11163229
references: Carcinogenesis. 2000 Mar;21(3):505-15
references: 10688871
references: Cancer Res. 1986 Dec;46(12 Pt 1):6327-32
references: 3536078
references: Dev Dyn. 2004 Nov;231(3):474-88
references: 15376313