title: Restructuring dynamics of DU 145 and LNCaP prostate cancer spheroids.
abstract: Neoplastic cells acquire multidrug resistance as they assemble into multicellular spheroids. Image analysis and Monte Carlo simulation provided an insight into the adhesion and motility events during spheroid restructuring in liquid-overlay culture of DU 145 and LNCaP human prostate cancer cells. Irregularly shaped, two-dimensional aggregates restructured through incremental cell movements into three-dimensional spheroids. Of the two cultures examined, restructuring was more pronounced for DU 145 aggregates. Motile DU 145 cells formed spheroids with a minimum cell overlay of 30% for 25-mers as estimated by simulation versus 5% for adhesive LNCaP cells in aggregates of the same size. Over 72 h, the texture ratio increased from 0.55 +/- 0.05 for DU 145 aggregates with projected areas exceeding 2000 microm2 to a value approaching 0.75 +/- 0.02 (P < 0.05). For LNCaP aggregates of comparable size, the increase in texture ratio was more modest, less than 15% during the same time period (P < 0.05). Combined, these data suggest that motility events govern the overall rate of spheroid restructuring. This information has application to the chemosensitization of solid tumors and kinetic modeling of spheroid production.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Lindy Boggs Center, Tulane University, New Orleans, Louisiana 70118, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Song
authors.forename: Shamik K
authors.initials: SK
authors.lastname: Jain
authors.forename: Richard M
authors.initials: RM
authors.lastname: Enmon
authors.forename: Kim C
authors.initials: KC
authors.lastname: O'Connor
mesh_terms: D002449:Cell Aggregation; D018929:Cell Culture Techniques; D002465:Cell Movement; D006801:Humans; D008297:Male; D009010:Monte Carlo Method; D011471:Prostatic Neoplasms; D018874:Spheroids, Cellular / Q000166:cytology* / Q000378:metabolism*; D014407:Tumor Cells, Cultured
references.citation: Biotechnol Bioeng. 2002 Dec 5;80(5):580-8
references.pmid: 12355469
references.citation: Proteins. 2000 Mar 1;38(4):414-27
references.pmid: 10707028
references.citation: Eur J Cancer. 2003 Jan;39(2):136-46
references.pmid: 12509944
references.citation: Tissue Eng. 2002 Dec;8(6):1071-81
references.pmid: 12542952
references.citation: Med Phys. 2003 Feb;30(2):144-57
references.pmid: 12607832
references.citation: Cancer. 1996 May 1;77(9):1862-72
references.pmid: 8646686
references.citation: Cancer Res. 2002 Mar 1;62(5):1266-70
references.pmid: 11888888
references.citation: Int J Cancer. 1987 Oct 15;40(4):557-63
references.pmid: 3478309
references.citation: J Cancer Res Clin Oncol. 1995;121(4):193-202
references.pmid: 7751317
references.citation: CA Cancer J Clin. 2003 Jan-Feb;53(1):5-26
references.pmid: 12568441
references.citation: Pharm Res. 1999 Apr;16(4):486-93
references.pmid: 10227701
references.citation: J Theor Biol. 1978 Mar 7;71(1):103-40
references.pmid: 642518
references.citation: Biotechnol Prog. 2003 Nov-Dec;19(6):1742-9
references.pmid: 14656150
references.citation: Curr Oncol Rep. 2003 May;5(3):250-7
references.pmid: 12667424
references.citation: Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):471-6
references.pmid: 9892657
references.citation: J Urol. 2001 Jan;165(1):130-5
references.pmid: 11125381
references.citation: Int J Cancer. 1998 Mar 16;75(6):855-63
references.pmid: 9506530
references.citation: Biophys J. 1992 Jan;61(1):119-28
references.pmid: 1540685
references.citation: Anticancer Res. 1998 Nov-Dec;18(6A):4147-58
references.pmid: 9891460
references.citation: Biotechnol Bioeng. 2001 Mar 20;72(6):579-91
references.pmid: 11460249
references.citation: Cancer Lett. 1991 Nov;60(2):113-9
references.pmid: 1933835
references.citation: Cancer Commun. 1991 Aug;3(8):255-64
references.pmid: 1653586
references.citation: Cancer Res. 1977 Oct;37(10):3639-43
references.pmid: 908012
references.citation: In Vitro Cell Dev Biol Anim. 1997 May;33(5):344-51
references.pmid: 9196892
references.citation: J Natl Cancer Inst. 1996 Sep 18;88(18):1285-96
references.pmid: 8797768