A genetic strategy to overcome the senescence of primary meningioma cell cultures.
Even though meningiomas are the second most common brain tumor in adults, little is known about the molecular basis of their growth and development. The lack of suitable cell culture model systems is an impediment to this understanding. Most studies on meningiomas rely on primary, early passage cell lines that eventually senesce or a few established cell lines that have been derived from aggressive variants of meningiomas. We have isolated three primary meningioma cell lines that are negative for telomerase activity. We can overcome the senescence of a Grade III derived meningioma cell line by expressing the telomerase catalytic subunit (hTERT), whereas Grade I meningioma cell lines require the expression of the human papillomavirus E6 and E7 oncogenes in conjunction with hTERT. Meningioma cell lines, immortalized in this manner, maintain their pre-transfection morphology and form colonies in vitro. We have confirmed the meningothelial origin of these cell lines by assessing expression of vimentin and desmoplakin, characteristic markers for meningiomas. Additionally, we have karyotyped these cell lines using array CGH and shown that they represent a spectrum of the genetic diversity seen in primary meningiomas. Thus, these cell lines represent novel cellular reagents for investigating the molecular oncogenesis of meningiomas.
Brain Tumor Research Center, Department of Neurological Surgery, University of California, San Francisco, CA 94143, USA.
Gilson S
GS
Baia
Alison L
AL
Slocum
Jeanette D
JD
Hyer
Anjan
A
Misra
Nouzhan
N
Sehati
Scott R
SR
VandenBerg
Burt G
BG
Feuerstein
Dennis F
DF
Deen
Michael W
MW
McDermott
Anita
A
Lal
D014408:Biomarkers, Tumor / Q000378:metabolism*; D018929:Cell Culture Techniques / Q000379:methods; D045744:Cell Line, Tumor / Q000378:metabolism*; D016922:Cellular Senescence / Q000235:genetics* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051180:Desmoplakins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology*; D018014:Gene Transfer Techniques; D006801:Humans; D007621:Karyotyping; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000378:metabolism; D008579:Meningioma / Q000235:genetics* / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D027383:Papillomaviridae; D050725:Papillomavirus E7 Proteins / Q000378:metabolism; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D014162:Transfection / Q000379:methods; D014170:Transformation, Genetic / Q000235:genetics*; D014746:Vimentin / Q000378:metabolism
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D051180:Desmoplakins; C052603:E6 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D014746:Vimentin; D019098:Telomerase