In vivo monitoring of CD44+ cancer stem-like cells by γ-irradiation in breast cancer.
There is increasing evidence that cancer contains cancer stem cells (CSCs) that are capable of regenerating a tumor following chemotherapy or radiotherapy. CD44 and CD133 are used to identify CSCs. This study investigated non-invasive in vivo monitoring of CD44-positive cancer stem-like cells in breast cancer by γ-irradiation using molecular image by fusing the firefly luciferase (fLuc) gene with the CD44 promoter. We generated a breast cancer cell line stably expressing fLuc gene by use of recombinant lentiviral vector controlled by CD44 promoter (MCF7-CL). Irradiated MCF7-CL spheres showed upregulated expression of CD44 and CD133, by immunofluorescence and flow cytometry. Also, gene expression levels of CSCs markers in irradiated spheres were clearly increased. CD44+ CSCs increased fLuc expression and tumor growth in vivo and in vitro. When MCF7-CL was treated with siCD44 and irradiated, CD44 expression was inhibited and cell survival ratio was decreased. MCF7-CL subsets were injected into the mice and irradiated by using a cobalt-60 source. Then, in vivo monitoring was performed to observe the bioluminescence imaging (BLI). When breast cancer was irradiated, relative BLI signal was increased, but tumor volume was decreased compared to non-irradiated tumor. These results indicate that increased CD44 expression, caused by general feature of CSCs by irradiation and sphere formation, can be monitored by using bioluminescence imaging. This system could be useful to evaluate CD44- expressed CSCs in breast cancer by BLI in vivo as well as in vitro for radiotherapy.
Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
Mi Hyun
MH
Kim
Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
Min Hwan
MH
Kim
Division of Radiation Cancer Research/Research Center for Radio-Senescence, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
Kwang Seok
KS
Kim
Division of Radiation Cancer Research/Research Center for Radio-Senescence, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
Myung-Jin
MJ
Park
Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
Jae-Hoon
JH
Jeong
Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
Seung Woo
SW
Park
Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
Young Hoon
YH
Ji
Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
Kwang Il
KI
Kim
Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
Tae Sup
TS
Lee
Department of Microbiology, Chonnam National University College of Medicine, Gwangju, Republic of Korea.
Phil Youl
PY
Ryu
Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
Joo Hyun
JH
Kang
Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
Yong Jin
YJ
Lee
D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology*; D051927:CD24 Antigen / Q000096:biosynthesis / Q000528:radiation effects; D005260:Female; D005720:Gamma Rays; D064593:Heterografts; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis* / Q000528:radiation effects*; D008163:Luminescent Measurements / Q000379:methods; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods; D014411:Neoplastic Stem Cells / Q000276:immunology* / Q000378:metabolism / Q000528:radiation effects*
D051927:CD24 Antigen; C497889:CD24 protein, human; C497483:CD44 protein, human; D018960:Hyaluronan Receptors