Rapid selection and proliferation of CD133+ cells from cancer cell lines: chemotherapeutic implications.
Cancer stem cells (CSCs) are considered a subset of the bulk tumor responsible for initiating and maintaining the disease. Several surface cellular markers have been recently used to identify CSCs. Among those is CD133, which is expressed by hematopoietic progenitor cells as well as embryonic stem cells and various cancers. We have recently isolated and cultured CD133 positive [CD133+] cells from various cancer cell lines using a NASA developed Hydrodynamic Focusing Bioreactor (HFB) (Celdyne, Houston, TX). For comparison, another bioreactor, the rotary cell culture system (RCCS) manufactured by Synthecon (Houston, TX) was used. Both the HFB and the RCCS bioreactors simulate aspects of hypogravity. In our study, the HFB increased CD133+ cell growth from various cell lines compared to the RCCS vessel and to normal gravity control. We observed a +15-fold proliferation of the CD133+ cellular fraction with cancer cells that were cultured for 7-days at optimized conditions. The RCCS vessel instead yielded a (-)4.8-fold decrease in the CD133+cellular fraction respect to the HFB after 7-days of culture. Interestingly, we also found that the hypogravity environment of the HFB greatly sensitized the CD133+ cancer cells, which are normally resistant to chemo treatment, to become susceptible to various chemotherapeutic agents, paving the way to less toxic and more effective chemotherapeutic treatment in patients. To be able to test the efficacy of cytotoxic agents in vitro prior to their use in clinical setting on cancer cells as well as on cancer stem cells may pave the way to more effective chemotherapeutic strategies in patients. This could be an important advancement in the therapeutic options of oncologic patients, allowing for more targeted and personalized chemotherapy regimens as well as for higher response rates.
Kelly
Sarah E
SE
Department of Biochemistry and Microbiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, West Virginia, United States of America.
Di Benedetto
Altomare
A
Greco
Adelaide
A
Howard
Candace M
CM
Sollars
Vincent E
VE
Primerano
Donald A
DA
Valluri
Jagan V
JV
Claudio
Pier Paolo
PP
D000071916:AC133 Antigen; D015703:Antigens, CD; D000970:Antineoplastic Agents / Q000494:pharmacology; D019149:Bioreactors / Q000592:standards; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation / Q000379:methods*; D004354:Drug Screening Assays, Antitumor / Q000379:methods* / Q000592:standards; D006023:Glycoproteins; D006801:Humans; D018472:Hypogravity; D014411:Neoplastic Stem Cells / Q000166:cytology*; D010455:Peptides
D000071916:AC133 Antigen; D015703:Antigens, CD; D000970:Antineoplastic Agents; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides
Ernst Schering Found Symp Proc. 2006;(5):141-53
17939300
Cell Prolif. 2009 Apr;42(2):219-28
19222485
Science. 1992 Mar 27;255(5052):1707-10
1553558
Aviat Space Environ Med. 2007 Apr;78(4 Suppl):A26-37
17511296
J Cell Biochem. 2009 Jul 1;107(4):723-31
19415677
Hepatology. 2006 Jul;44(1):240-51
16799977
Proc Natl Acad Sci U S A. 2004 Jan 20;101(3):781-6
14711994
Nature. 2001 Nov 1;414(6859):105-11
11689955
J Clin Oncol. 2008 Jun 10;26(17):2890-4
18539969
Int J Artif Organs. 1999 Dec;22(12):816-22
10654878
Pediatr Res. 2006 Apr;59(4 Pt 2):59R-64R
16549550
Mol Interv. 2006 Jun;6(3):140-8
16809475
Biochim Biophys Acta. 2007 Jun;1775(2):283-97
17374555
Curr Neurol Neurosci Rep. 2007 May;7(3):215-20
17488587
Cell Prolif. 2009 Jun;42(3):385-93
19397591
Science. 1977 Jul 29;197(4302):461-3
560061
Semin Cancer Biol. 2007 Jun;17(3):214-8
16750389
Cancer. 2004 Feb 15;100(4):818-25
14770440
J Invest Dermatol. 2006 Jan;126(1):142-53
16417230
Neoplasma. 2005;52(6):435-40
16284686
Cell Mol Life Sci. 2007 Dec;64(24):3248-60
17955177
Nat Rev Cancer. 2005 Apr;5(4):275-84
15803154
J Cell Mol Med. 2008 Jan-Feb;12(1):67-96
18053092
J Neurosci. 1992 Nov;12(11):4565-74
1432110
Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8
12629218
Stem Cell Rev. 2007 Jun;3(2):169-75
17873349
Cancer Res. 2003 Sep 15;63(18):5821-8
14522905
PLoS One. 2008;3(10):e3469
18941626
J Antibiot (Tokyo). 1979 Oct;32(10):1038-45
528363
Pediatr Res. 2007 Sep;62(3):239
17712286
Nat Rev Cancer. 2008 Jun;8(6):465-72
18451812
Aviat Space Environ Med. 2008 Jun;79(6):629-35
18581950
Health Phys. 2003 Jul;85(1):94-102
12861962
Trends Cell Biol. 2005 Sep;15(9):494-501
16084092
Cancer Chemother Rep. 1968 Feb;52(2):251-5
5646852
Pharm Weekbl Sci. 1985 Oct 25;7(5):173-80
3906559
J Cell Physiol. 2008 Aug;216(2):332-6
18459113
Cancer Cell Int. 2007 Sep 10;7:14
17845729
Cancer Treat Rep. 1981;65 Suppl 1:3-12
7326663
Lab Invest. 2008 May;88(5):459-63
18379567
Cancer Res. 2005 Dec 1;65(23):10946-51
16322242
J Clin Oncol. 2008 Jun 10;26(17):2883-9
18539968
J Clin Oncol. 2008 Jun 10;26(17):2862-70
18539965
Cancer Res. 2006 Jul 15;66(14):7341-7
16849585
J Clin Oncol. 2008 Jun 10;26(17):2806-12
18539958
Proc Natl Acad Sci U S A. 2004 Sep 28;101(39):14228-33
15381773
Cell Res. 2008 May;18(5):528-37
18414448
Biotechnol Bioeng. 2009 Mar 1;102(4):1242-50
18949761
J Surg Oncol. 2001 Nov;78(3):162-70
11745799
Mutat Res. 1999 Dec 6;430(2):255-69
10631340
Adv Space Res. 1992;12(2-3):195-200
11537008
J Natl Compr Canc Netw. 2007 Apr;5(4):449-55
17442235
J Orthop Res. 2009 Apr;27(4):517-21
18932231
Neoplasia. 2005 Nov;7(11):967-76
16331882
Gene Ther. 2008 Nov;15(21):1446-53
18596829
Cancer Invest. 2001;19(3):292-315
11338887
J Pathol. 2008 Jan;214(1):3-9
18067118
Ann N Y Acad Sci. 2006 Dec;1091:470-89
17341637
Expert Rev Mol Diagn. 2008 Jul;8(4):387-93
18598221
Stem Cell Rev. 2008 Sep;4(3):211-6
18663609