Preclinical platform of retinoblastoma xenografts recapitulating human disease and molecular markers of dissemination.
Translational research in retinoblastoma - a pediatric tumor that originates during the development of the retina - would be improved by the creation of new patient-derived models. Using tumor samples from enucleated eyes we established a new battery of preclinical models that grow in vitro in serum-free medium and in vivo in immunodeficient mice. To examine whether the new xenografts recapitulate human disease and disseminate from the retina to the central nervous system, we evaluated their histology and the presence of molecular markers of dissemination that are used in the clinical setting to detect extraocular metastases. We evaluated GD2 synthase and CRX as such markers and generated a Taqman real-time quantitative PCR method to measure CRX mRNA for rapid, sensitive and specific quantification of local and metastatic tumor burden. This approach was able to detect 1 human retinoblastoma cell in 100.000 mouse brain cells. Our research adds novel preclinical tools for the discovery of new retinoblastoma treatments for clinical translation.
Developmental Tumor Biology Laboratory, Fundacio Sant Joan de Deu, Barcelona, Spain; Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, Barcelona, Spain.
Guillem
G
Pascual-Pasto
Developmental Tumor Biology Laboratory, Fundacio Sant Joan de Deu, Barcelona, Spain; Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, Barcelona, Spain.
Nagore G
NG
Olaciregui
Developmental Tumor Biology Laboratory, Fundacio Sant Joan de Deu, Barcelona, Spain; Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, Barcelona, Spain.
Monica
M
Vila-Ubach
Developmental Tumor Biology Laboratory, Fundacio Sant Joan de Deu, Barcelona, Spain; Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, Barcelona, Spain.
Sonia
S
Paco
Developmental Tumor Biology Laboratory, Fundacio Sant Joan de Deu, Barcelona, Spain; Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, Barcelona, Spain.
Carles
C
Monterrubio
Developmental Tumor Biology Laboratory, Fundacio Sant Joan de Deu, Barcelona, Spain; Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, Barcelona, Spain.
Eva
E
Rodriguez
Pathology, Hospital Sant Joan de Deu, Barcelona, Spain; Clinical Pharmacokinetics Unit, Hospital de Pediatria JP Garrahan, Buenos Aires, Argentina.
Ursula
U
Winter
Developmental Tumor Biology Laboratory, Fundacio Sant Joan de Deu, Barcelona, Spain.
Mireia
M
Batalla-Vilacis
Ophthalmology, Hospital Sant Joan de Deu, Barcelona, Spain.
Jaume
J
Catala
Developmental Tumor Biology Laboratory, Fundacio Sant Joan de Deu, Barcelona, Spain; Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, Barcelona, Spain.
Hector
H
Salvador
Developmental Tumor Biology Laboratory, Fundacio Sant Joan de Deu, Barcelona, Spain; Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, Barcelona, Spain.
Andreu
A
Parareda
Clinical Pharmacokinetics Unit, Hospital de Pediatria JP Garrahan, Buenos Aires, Argentina; CONICET, Buenos Aires, Argentina.
Paula
P
Schaiquevich
Pathology, Hospital Sant Joan de Deu, Barcelona, Spain.
Mariona
M
Suñol
Developmental Tumor Biology Laboratory, Fundacio Sant Joan de Deu, Barcelona, Spain; Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, Barcelona, Spain.
Jaume
J
Mora
Developmental Tumor Biology Laboratory, Fundacio Sant Joan de Deu, Barcelona, Spain; Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, Barcelona, Spain.
Cinzia
C
Lavarino
Developmental Tumor Biology Laboratory, Fundacio Sant Joan de Deu, Barcelona, Spain; Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, Barcelona, Spain.
Carmen
C
de Torres
Developmental Tumor Biology Laboratory, Fundacio Sant Joan de Deu, Barcelona, Spain; Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, Barcelona, Spain; CONICET, Buenos Aires, Argentina; Garrahan Research Institute, Hospital de Pediatria JP Garrahan, Buenos Aires, Argentina.
Guillermo L
GL
Chantada
Developmental Tumor Biology Laboratory, Fundacio Sant Joan de Deu, Barcelona, Spain; Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, Barcelona, Spain. Electronic address: amontero@fsjd.org.
Angel M
AM
Carcaboso
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001932:Brain Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement; D002675:Child, Preschool; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008819:Mice, Nude; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D061206:Neoplasm Micrometastasis; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D019572:Retinal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D012175:Retinoblastoma / Q000201:enzymology* / Q000235:genetics / Q000556:secondary; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; C109288:cone rod homeobox protein; D017350:N-Acetylgalactosaminyltransferases; C023220:(N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase
CRX; Metastasis; Retinoblastoma; Tumor model; Xenograft