Identification and characterization of cancer stem-like cells from primary carcinoma of the cervix uteri.
Like many other solid tumors, cervical cancer contains a heterogeneous population of cancer cells. Several investigators have identified putative stem cells from solid tumors and cancer cell lines via the capacity to self renew and drive tumor formation. The aim of this study was to identify and characterize a cancer stem-like cell population from primary carcinoma of the cervix uteri. Cervical carcinoma from 19 patients staged I-II following International Federation of Gynecology and Obstetrics (FIGO) criteria were disaggregated and subjected to growth conditions selective for stem cells. Eight of nineteen tumor-derived cultures encompassed stem-like cells capable of self-renewal, extensive proliferation as clonal non-adherent spherical clusters. Cell markers of spheroid were identified as CD44+CK17+. Cell survival assays showed the sphere-forming cells were only 48% inhibited by doxorubicin whereas 78% inhibited by paclitaxel. Chemo-resistance may partly attribute to the exclusive expression of ABC transporter. To investigate the tumorigenicity of these stem-like cells, xenoengraftment of 10(5) dissociated spheroid cells allowed full recapitulation of the original tumor, whereas the same amount of tumor cells without non-adherent spheroid selection remained non-tumorigenic. Stemness properties of these spheroid cells were further established by reverse transcription-PCR and Western blotting, demonstrating the expression of embryonic and adult stemness-related genes (Oct-4, Piwil2, C-myc, Stat3 and Sox2). Based on these findings, we assert that cervical cancer contain a subpopulation of tumor initiating cells with stem-like properties, thus facilitating the approach to therapeutic strategies aimed at eradicating the tumorigenic subpopulation within cervical cancer.
Anhui Province Key Laboratory of Molecular Medicine, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, PR China.
Dingqing
D
Feng
Cheng
C
Peng
Cairong
C
Li
Ying
Y
Zhou
Min
M
Li
Bin
B
Ling
Haiming
H
Wei
Zhigang
Z
Tian
D000328:Adult; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007097:Imines / Q000378:metabolism; D007124:Immunoenzyme Techniques; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D017239:Paclitaxel / Q000008:administration & dosage; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D013843:Thiazines / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*
D018960:Hyaluronan Receptors; D007097:Imines; D013843:Thiazines; D004317:Doxorubicin; C091704:CK 17; D017239:Paclitaxel