Establishment of atypical-teratoid/rhabdoid tumor (AT/RT) cell cultures from disseminated CSF cells: a model to elucidate biology and potential targeted therapeutics.
Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant central nervous system neoplasm that usually affects infants and young children. In this report, we describe culture conditions that enabled the sustained growth of tumor cells obtained from the cerebrospinal fluid (CSF) of an infant with AT/RT. These cells retained the morphological and biomarker characteristics of the original tumor. A screening of receptor tyrosine kinases identified the presence of phosphorylated ErbB4, Insulin-R, PDGFR and IGF-IR, which appear to depend on Hsp90 to maintain their active form. IGF-IR activity is consistent with data from other established AT/RT cell lines. Inhibition of IGF-IR by the small molecular weight inhibitor AEW541 led to growth suppression of cultured AT/RT cells. In addition, neutralizing antibodies to IGF-II also inhibited the growth of these cells suggesting a potential autocrine function for this cytokine. We also compared cultured AT/RT cells to established cell lines to identify consistent drug sensitivity patterns among these cells. In addition to previously described cell lines and xenograft models, continuous culture of CSF derived cells may also provide an effective way to study the biology of AT/RT and to identify potential targets for future therapeutics for this tumor.
Narendran
Aru
A
Translational Research Laboratories, Southern Alberta Children's Cancer Program, The University of Calgary, Calgary, AB, Canada. a.narendran@ucalgary.ca
Coppes
Lucas
L
Jayanthan
Aarthi
A
Coppes
Michael
M
Teja
Bijan
B
Bernoux
Delphine
D
George
David
D
Strother
Douglas
D
D000199:Actins / Q000378:metabolism; D049109:Cell Proliferation; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007223:Infant; D020128:Inhibitory Concentration 50; D008297:Male; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D018335:Rhabdoid Tumor / Q000134:cerebrospinal fluid* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000473:pathology; D014746:Vimentin / Q000378:metabolism
D000199:Actins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D009687:Nuclear Proteins; D010975:Platelet Aggregation Inhibitors; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors; D014746:Vimentin; D020794:Receptor Protein-Tyrosine Kinases