Establishment of human tumoral ependymal cell lines and coculture with tubular-like human endothelial cells.
Ependymomas, rare neoplasms of the central nervous system, occur predominantly in children. They are highly vascularized, and histological findings show many perivascular rosettes of tumoral cells radially organized around capillaries. Treatment of ependymomas relies on surgery combined with radio- or chemotherapy, but the efficiency of chemotherapy is limited, probably because of their multidrug resistance (MDR) phenotype. Progress in the therapy of these neoplasms is dramatically limited by the absence of cell line models. We established conditions for the long-term culture of human tumoral ependymocytes and their 3D coculture in Matrigel with endothelial cells. Histological, immunological, and ultrastructural studies showed that the morphological features (microvilli, cilia, and caveolae) of these cultured cells were similar to those of the tumor in vivo. The cells expressed potential oncological markers related to the immature state of tumoral cells (nestin and Notch-1), their tumorigenicity [caveolae and epidermal growth factor-receptor (EGF-R)], or the MDR phenotype [P-glycoprotein (P-gp)]. The expression of P-gp, EGF-R, and caveolin-1 by these tumoral ependymocytes could be useful in studies on new drugs. This coculture model might represent a new powerful tool to study new therapeutic delivery strategies in tumoral cells.
Brisson
C
C
Inserm U433, Faculté de Médecine R. Laennec, F-69372 Lyon, Cedex 08, France. brisson@laennec.univ-lyon1.fr
Lelong-Rebel
I
I
Mottolèse
C
C
Jouvet
A
A
Fèvre-Montange
M
M
Saint Pierre
G
G
Rebel
G
G
Belin
M F
MF
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D018929:Cell Culture Techniques / Q000379:methods*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D018920:Coculture Techniques; D003094:Collagen / Q000494:pharmacology; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000166:cytology*; D004806:Ependymoma / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007797:Laminin / Q000494:pharmacology; D008297:Male; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D011509:Proteoglycans / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins / Q000166:cytology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen