Novel cell lines established from pediatric brain tumors |
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| Authors: | Jingying Xu Anat Erdreich-Epstein Ignacio Gonzalez-Gomez Elizabeth Y. Melendez Goar Smbatyan Rex A. Moats Michael Rosol Jaclyn A. Biegel C. Patrick Reynolds |
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| Affiliation: | (1) Developmental Therapeutics Program, Division of Hematology-Oncology, USC-CHLA Institute for Pediatric Clinical Research, Children’s Hospital Los Angeles, Los Angeles, CA 90027, USA;(2) Children’s Hospital Los Angeles, Los Angeles, CA 90027, USA;(3) Department of Pediatrics and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA;(4) Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA;(5) Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA;(6) Division of Hematology-Oncology, Children’s Hospital Los Angeles, Los Angeles, CA 90027, USA;(7) Division of Human Genetics, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA;(8) Cancer Center, School of Medicine, Texas Tech University Health Sciences Center, 3601 4th Street, Stop 9445, Lubbock, TX 79430, USA; |
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| Abstract: | The paucity of cell culture models for childhood brain tumors prompted us to establish pediatric cell lines for use in biological
experiments and preclinical developmental therapeutic studies. Three cell lines were established, CHLA-200 (GBM), CHLA-259
(anaplastic medulloblastoma) and CHLA-266 (atypical teratoid rhabdoid tumor, AT/RT). Consistent with an AT/RT origin, CHLA-266
lacked INI1 expression and had monosomy 22. All lines had unique DNA short tandem repeat “fingerprints” matching that of the
patient’s tumor tissue and were adherent on tissue culture plastic, but differed in morphology and doubling times. CHLA-200
had a silent mutation in TP53. CHLA-259 and CHLA-266 had wild-type TP53. All three lines were relatively resistant to multiple drugs when compared to the DAOY medulloblastoma cell line, using the
DIMSCAN fluorescence digital image microscopy cytotoxicity assay. RNA expression of MYC and MYCN were quantified using RT-PCR
(Taqman). CHLA-200 expressed MYC, DAOY and CHLA-259 expressed MYCN, and CHLA-266 expressed both MYCN and MYC. CHLA-200 was
only tumorigenic subcutaneously, but CHLA-259 and CHLA-266 were tumorigenic both subcutaneously and in brains of NOD/SCID
mice. Immunohistochemistry of the xenografts revealed GFAP staining in CHLA-200 and PGP 9.5 staining in CHLA-259 and CHLA-266
tumors. As expected, INI1 expression was lacking in CHLA-266 (AT/RT). These three new cell lines will provide useful models
for research of pediatric brain tumors. |
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