개 REM134 유선종양세포의 sphere 형성을 통한 암 줄기세포 특성 분석 = Tumorsphere formation and cancer stem cell characterization of REM134 canine mammary carcinoma cells

다국어 초록 (Multilingual Abstract)

Canine mammary tumors are among the most frequently observed cutaneous tumors in female dogs. Cancer stem cells (CSCs), referred to as tumor-initiating cells, are thought to have properties similar to normal stem cells such as the ability to self-renewal and to differentiate into various cell types. Biological understanding of CSCs and the critical pathways involved in their maintenance are important in research and therapy for mammary tumors. We conducted the present study on sphere formation from REM134 cells by using methylcellulose to produce tumorspheres on a large scale and compared the specific markers of the spheres-formed and plating-cultured REM134 cells. The results revealed that the tumorspheres cultured in methylcellulose had higher seeding density and improved morphology compared to those produced in normal sphere formation medium. Expression levels of stemness markers and CSC-related markers were higher in tumorsphere-forming cells than in plating-cultured cells. Subsequently, we transplanted the tumorsphere-forming and plating-cultured cells into female nude mice to examine their tumorigenic potential. Tumor volume increased rapidly in mice transplanted with tumorsphere-derived cells compared to plating-cultured cells. We observed a novel sphere-forming condition for REM134 cells and showed that REM134 cell tumorspheres can exhibit improved CSC properties.

참고문헌 (Reference)

• 1 Pang LY, "Using naturally occurring tumours in dogs and cats to study telomerase and cancer stem cell biology" 1792 : 380-391, 2009
• 2 Chen K, "Understanding and targeting cancer stem cells: therapeutic implications and challenges" 34 : 732-740, 2013
• 3 Dean M, "Tumour stem cells and drug resistance" 5 : 275-284, 2005
• 4 Lee CH, "Tumorsphere as an effective in vitro platform for screening anti-cancer stem cell drugs" 7 : 1215-1226, 2016
• 5 Korsching E, "The origin of vimentin expression in invasive breast cancer:epithelial-mesenchymal transition, myoepithelial histogenesis or histogenesis from progenitor cells with bilinear differentiation potential?" 206 : 451-457, 2005
• 6 Else RW, "The characteristics of a canine mammary carcinoma cell line, REM 134" 46 : 675-681, 1982
• 7 Reya T, "Stem cells, cancer, and cancer stem cells" 414 : 105-111, 2001
• 8 Bapat SA, "Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer" 65 : 3025-3029, 2005
• 9 MacEwen EG, "Spontaneous tumors in dogs and cats: models for the study of cancer biology and treatment" 9 : 125-136, 1990
• 10 Weiswald LB, "Spherical cancer models in tumor biology" 17 : 1-15, 2015
• 11 Torres CG, "Simvastatin exhibits antiproliferative effects on spheres derived from canine mammary carcinoma cells" 33 : 2235-2244, 2015
• 12 Yang ZF, "Significance of CD90+cancer stem cells in human liver cancer" 13 : 153-166, 2008
• 13 Al-Hajj M, "Prospective identification of tumorigenic breast cancer cells" 100 : 3983-3988, 2003
• 14 Timmermans-Sprang EPM, "Molecular signaling of progesterone, growth hormone, Wnt, and HER in mammary glands of dogs, rodents, and humans: new treatment target identification" 4 : 53-, 2017
• 15 Cocola C, "Isolation of canine mammary cells with stem cell properties and tumourinitiating potential" 44 : 214-217, 2009
• 16 Wilson H, "Isolation and characterisation of cancer stem cells from canine osteosarcoma" 175 : 69-75, 2008
• 17 Takahashi K, "Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors" 126 : 663-676, 2006
• 18 Dontu G, "In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells" 17 : 1253-1270, 2003
• 19 Geraldes M, "Immunohistochemical study of hormonal receptors and cell proliferation in normal canine mammary glands and spontaneous mammary tumors" 146 : 403-406, 2000
• 20 Magalhães GM, "Immunodetection of cells with a CD44+/CD24− phenotype in canine mammary neoplasms" 9 : 205-, 2013
• 21 Schatton T, "Identification of cells initiating human melanomas" 451 : 345-349, 2008
• 22 Ricci-Vitiani L, "Identification and expansion of human colon-cancer-initiating cells" 445 : 111-115, 2007
• 23 Bonnet D, "Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell" 3 : 730-737, 1997
• 24 Bao S, "Glioma stem cells promote radioresistance by preferential activation of the DNA damage response" 444 : 756-760, 2006
• 25 Rutteman GR, "Expression of epidermal growth factor receptor (EGFR) in nonaffected and timorous mammary tissue of female dogs" 30 : 139-146, 1994
• 26 Murai K, "Establishment of a pair of novel cloned tumour cell lines with or without metastatic potential from canine mammary adenocarcinoma" 93 : 468-472, 2012
• 27 Fan X, "Effective enrichment of prostate cancer stem cells from spheres in a suspension culture system" 30 : 314-318, 2012
• 28 Kol A, "Companion animals: translational scientist’s new best friends" 7 : 308ps21-, 2015
• 29 Michishita M, "Characterization of spheres derived from canine mammary gland adenocarcinoma cell lines" 91 : 254-260, 2011
• 30 Pinho SS, "Canine tumors: a spontaneous animal model of human carcinogenesis" 159 : 165-172, 2012
• 31 Dobson JM, "Canine neoplasia in the UK: estimates of incidence rates from a population of insured dogs" 43 : 240-246, 2002
• 32 Sorenmo K, "Canine mammary gland tumors" 33 : 573-596, 2003
• 33 Pang LY, "Canine mammary cancer stem cells are radio- and chemo-resistant and exhibit an epithelial-mesenchymal transition phenotype" 3 : 1744-1762, 2011
• 34 Blacking TM, "CD44 is associated with proliferation, rather than a specific cancer stem cell population, in cultured canine cancer cells" 141 : 46-57, 2011
• 35 Livak KJ, "Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method" 25 : 402-408, 2001
• 36 Zhu ZW, "A novel three-dimensional tumorsphere culture system for the efficient and low-cost enrichment of cancer stem cells with natural polymers" 15 : 85-92, 2018
• 37 O’Brien CA, "A human colon cancer cell capable of initiating tumour growth in immunodeficient mice" 445 : 106-110, 2007