In vitro and in vivo properties of CD133 expressing cells from human lung cancer cell lines

Experimental Hematology & Oncology

Gunnar Kvalheim²  Gustav Gaudernack²  Øystein Fodstad²  Hanne K Høifødt¹  Mengyu Wang⁴  Zhenhe Suo²  Ping Wang³ 

[1] Department of Tumor Biology, Institute of Cancer Research, Oslo University Hospital, Radiumhospitalet, Oslo, Norway;Faculty of Medicine, University of Oslo, Oslo, Norway;Department of Hematology, Henan Tumor Hospital, Zhengzhou, P. R. China;Department of Cellular Therapy, Oslo University Hospital, Radiumhospitalet, Oslo, Norway

关键词: Side population;    CD44;    CD133;    Lung cancer cell lines;    Cancer stem cells;   

Others  :  812248
DOI  :  10.1186/2162-3619-2-16

 received in 2013-04-14, accepted in 2013-05-30,  发布年份 2013

【 摘 要 】

Background

Tumor development is recently hypothesized to depend on a rare cell population with stem cell properties, such cells are called cancer stem cells (CSCs) or tumor-initiating cells (TICs). From various cancer tissues or cancer cell lines, CD133 expressing cells were found to define a unique CSC/TIC phenotype. To study whether that also could be the case in lung cancer, we examined different lung cancer cell lines for CD133 expression.

Results

Among the 4 cell lines studied, only the cell line LC-42 expressed CD133. Therefore, LC-42 was further characterized and studied with special emphasis on identifying the presence of CD133⁺ CSCs/TICs. FACS sorted CD133^high and CD133^dim subpopulations from LC-42 showed no differences in soft agar colony-forming capacity and spheres-forming capacity in serum-free cultures. LC-42 cells contained Side Population (SP), and only SP cells were able to form spheres. Furthermore, Nanog expression was significantly higher in SP than in non-SP. However, no difference was observed of CD133 expression in SP and non-SP. When CD133^high and CD133^dim cells were serially xeno-transplanted in NOD/SCID mice, both formed tumours similar to their parental LC-42 cells. There were no expression differences for NANOG, OCT4 and SOX2 examined immunohistochemically in the xenografts from both cell fractions.

Conclusion

Our data do not show a difference in tumorigenic potential of CD133^high and CD133^dim cells with respect to any of the parameters analyzed in vitro and in vivo, suggesting that CD133 expression is not restricted to cancer-initiating cells in the human lung cancer cell line LC-42.

【 授权许可】

   
2013 Wang et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 3.

【 参考文献 】

• [1]SEER (Surveillance, Epidemiology, and End Results, NCI) Lung and Bronchus: Stat Fact Sheets; 2012. http://seer.cancer.gov/statfacts/html/lungb.html webcite
• [2]Hamburger AW, Salmon SE: Primary bioassay of human tumor stem cells. Science 1977, 197:461-463.
• [3]Reya T, Morrison SJ, Clarke MF, et al.: Stem cells, cancer, and cancer stem cells. Nature 2001, 414:105-11.
• [4]Lapidot T, Sirard C, Vormoor J, et al.: A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 1994, 367:645-648.
• [5]Bonnet D, Dick JE: Human acute myeloid leukaemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 1997, 3:730-737.
• [6]Al Hajj M, Wicha MS, Ito Hernandez A, et al.: Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 2003, 100:3983-3988.
• [7]Singh SK, Hawkins C, Clarke ID, et al.: Identification of human brain tumour initiating cells. Nature 2004, 432:396-401.
• [8]Fang D, Nguyen TK, Leishear K, et al.: A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res 2005, 65:9328-9337.
• [9]Ricci-Vitiani L, Lombardi DG, Pilozzi E, et al.: Identification and expansion of human colon-cancer-initiating cells. Nature 2007, 445:111-115.
• [10]O'Brien CA, Pollett A, Gallinger S, et al.: A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2007, 445:106-110.
• [11]Hermann PC, Huber SL, Herrler T, et al.: Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 2007, 1:313-323.
• [12]Li C, Heidt D, Dalerba P, et al.: Identification of pancreatic cancer stem cells. Cancer Res 2007, 67:1030-1037.
• [13]Collins AT, Berry PA, Hyde C, et al.: Prospective Identification of Tumorigenic Prostate Cancer Stem Cells. Cancer Res 2005, 65:10946-10951.
• [14]Prince ME, Sivanandan R, Kaczorowski A, et al.: Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA 2007, 104:973-978.
• [15]Kim CF, Jackson EL, Woolfenden AE, et al.: Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 2005, 121:823-835.
• [16]Yin AH, Miraglia S, Zanjani ED, et al.: AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 1997, 90:5002-5012.
• [17]Salven P, Mustjoki S, Alitalo R, et al.: VEGFR-3 and CD133 identify a population of CD34+ lymphatic/vascular endothelial precursor cells. Blood 2003, 101:168-172.
• [18]Uchida N, Buck DW, He D, et al.: Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci USA 2000, 97:14720-14725.
• [19]Monzani E, Facchetti F, Galmozzi E, et al.: Melanoma contains CD133 and ABCG2 positive cells with enhanced tumourigenic potential. Eur J Cancer 2007, 43:935-946.
• [20]Eramo A, Lotti F, Sette G, et al.: Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ 2008, 15:504-514.
• [21]LaBarge MA, Bissell MJ: Is CD133 a marker of metastatic colon cancer stem cells? J Clin Invest 2008, 118:2021-2024.
• [22]Shmelkov SV, Butler JM, Hooper AT, et al.: CD133 expression is not restricted to stem cells, and both CD133+ and CD133ГÇô metastatic colon cancer cells initiate tumors. J Clin Invest 2008, 118:2111-2120.
• [23]Hirschmann-Jax C, Foster AE, Wulf GG, et al.: A distinct side population of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci USA 2004, 101:14228-14233.
• [24]Suetsugu A, Nagaki M, Aoki H, et al.: Characterization of CD133+ hepatocellular carcinoma cells as cancer stem//progenitor cells. Biochem Biophys Res Commun 2006, 351:820-824.
• [25]Elsaba TM, Martinez-Pomares L, Robins AR, et al.: The stem cell marker CD133 associates with enhanced colony formation and cell motility in colorectal cancer. PLoS One 2010, 5:e10714.
• [26]Corbeil D, Roper K, Hellwig A, et al.: The human AC133 hematopoietic stem cell antigen is also expressed in epithelial cells and targeted to plasma membrane protrusions. J Biol Chem 2000, 275:5512-5520.
• [27]Leung EL, Fiscus RR, Tung JW, et al.: Non-Small Cell Lung Cancer Cells Expressing CD44 Are Enriched for Stem Cell-Like Properties. PLoS One 2010, 5:e14062.
• [28]Yu J, Vodyanik MA, Smuga-Otto K, et al.: Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells. Science 2007, 318:1917-1920.
• [29]Thiery JP: Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2002, 2:442-454.
• [30]Mani SA, Guo W, Liao MJ, et al.: The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008, 133:704-715.
• [31]Zhou S, Schuetz JD, Bunting KD, et al.: The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med 2001, 7:1028-1034.
• [32]Kondo T, Setoguchi T, Taga T: Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc Natl Acad Sci USA 2004, 101:781-786.
• [33]Chiba T, Kita K, Zheng YW, et al.: Side population purified from hepatocellular carcinoma cells harbors cancer stem cell like properties. Hepatology 2006, 44:240-251.
• [34]Haraguchi N, Utsunomiya T, Inoue H, et al.: Characterization of a Side Population of Cancer Cells from Human Gastrointestinal System. Stem Cells 2006, 24:506-513.
• [35]Szotek PP, Pieretti-Vanmarcke R, Masiakos PT, et al.: Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness. Proc Natl Acad Sci USA 2006, 103:11154-11159.
• [36]Ho MM, Ng AV, Lam S, et al.: Side Population in Human Lung Cancer Cell Lines and Tumors Is Enriched with Stem-like Cancer Cells. Cancer Res 2007, 67:4827-4833.
• [37]Myklebust AT, Pharo A, Fodstad O: Effective removal of SCLC cells from human bone marrow. Use of four monoclonal antibodies and immunomagnetic beads. Br J Cancer 1993, 67:1331-1336.