Side population in the pancreatic cancer cell lines SW1990 and CFPAC-1 is enriched with cancer stem-like cells.
In this study, we first sought to determine the existence of side population (SP) cells in pancreatic cancer cell lines. Furthermore, we compared the biological characteristics of SP and non-SP cells. The presence of side population cells in pancreatic cancer cell lines was detected by Hoechst 33342 staining and FACS analysis. Cell cycle distribution was analyzed using flow cytometry. SP and non-SP cells were exposed to various concentrations of gemcitabine; drug sensitivity was examined using the MTT assay and flow cytometry using Annexin-V and PI staining. To compare the tumorigenic ability in vivo, groups of nude mice were orthotopically inoculated with varying numbers of SP and non-SP cells. The percentages of CD44+CD24+ and CD133+ in SP and non-SP cells were also detected by FACS analysis. The SP fraction was detected in BxPc-3, CFPAC-1, MIA PaCa-2, PANC-1 and SW1990 pancreatic cancer cell lines. Cell cycle analysis revealed that the SP cells contained more cells in the G1 phase and fewer cells in the S phase when compared with the non-SP cells. The SP cells exhibited increased tumorigenetic ability following in vivo transplantation into BALB/C nude mice and increased chemoresistance following in vitro exposure to gemcitabine. FACS analysis showed that the SP cells contained more CD44+CD24+ and CD133+ cells than the non-SP cells. In conclusion, these observations suggest that SP cells in the pancreatic cancer cell lines possess the property of cancer stem cells. SP cells may therefore be novel specific targets for the effective treatment of pancreatic cancer.
Yao
Jie
J
Laboratory of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China.
Cai
Hui-Hua
HH
Wei
Ji-Shu
JS
An
Yong
Y
Ji
Zhen-Ling
ZL
Lu
Zi-Peng
ZP
Wu
Jun-Li
JL
Chen
Ping
P
Jiang
Kui-Rong
KR
Dai
Cun-Cai
CC
Qian
Zhu-Yin
ZY
Xu
Ze-Kuan
ZK
Miao
Yi
Y
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis; D051927:CD24 Antigen / Q000032:analysis; D002453:Cell Cycle; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D010455:Peptides / Q000032:analysis; D013997:Time Factors; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
D000071916:AC133 Antigen; D015703:Antigens, CD; D000964:Antimetabolites, Antineoplastic; D051927:CD24 Antigen; C497889:CD24 protein, human; C497483:CD44 protein, human; D006023:Glycoproteins; D018960:Hyaluronan Receptors; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D003841:Deoxycytidine; D000093542:Gemcitabine