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Comprehensive establishment and characterization of orthoxenograft mouse models of malignant peripheral nerve sheath tumors for personalized medicine.

Castellsagué J, Gel B, Fernández-Rodríguez J, Llatjós R, Blanco I, Benavente Y, Pérez-Sidelnikova D, García-Del Muro J, Viñals JM, Vidal A, Valdés-Mas R, Terribas E, López-Doriga A, Pujana MA, Capellá G, Puente XS, Serra E, Villanueva A, Lázaro C - EMBO Mol Med (2015)

Bottom Line: These aggressive malignancies confer poor survival, with no effective therapy available.Our work points to differences in the engraftment process of primary tumors compared with the engraftment of established cell lines.Sorafenib (a BRAF inhibitor), in combination with doxorubicin or rapamycin, was found to be the most effective treatment for reducing MPNST growth.

View Article: PubMed Central - PubMed

Affiliation: Hereditary Cancer Program, Catalan Institute of Oncology (ICO-IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain Translational Research Laboratory ICO-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.

No MeSH data available.


Related in: MedlinePlus

Development of orthoxenograft mouse models of MPNSTsFive orthotopic xenograft mice models were established from four different MPNSTs and one cell line. Two of the MPNSTs come from the same NF1 patient; the other two were sporadic cases. Primary tumor (2–3 mm3) or tumor cell line (3 × 106 cells) were grafted or injected in the leg of athymic nude mice, close to the sciatic nerve. Tumors were perpetuated along several passages and subsequently expanded. Several assays were performed on tumors in early passages (histopathological analysis, gene expression profiling, genomic profiling, and drug efficacy studies). *NF1-MPNST-001 at passage 4 (P4) and all primary tumors and orthotopic tumors (OT) at passage 1 (P1) were analyzed by exome sequencing and immunohistochemistry. All primary tumors and orthotopic tumors at passages 1 and 4 were analyzed by expression array (except NF1-MPNST-001 PT, SP-MPNST-001 OT P4, and NF1-S462 OT P4). Copy number analysis (CNA) was performed in all samples.
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fig01: Development of orthoxenograft mouse models of MPNSTsFive orthotopic xenograft mice models were established from four different MPNSTs and one cell line. Two of the MPNSTs come from the same NF1 patient; the other two were sporadic cases. Primary tumor (2–3 mm3) or tumor cell line (3 × 106 cells) were grafted or injected in the leg of athymic nude mice, close to the sciatic nerve. Tumors were perpetuated along several passages and subsequently expanded. Several assays were performed on tumors in early passages (histopathological analysis, gene expression profiling, genomic profiling, and drug efficacy studies). *NF1-MPNST-001 at passage 4 (P4) and all primary tumors and orthotopic tumors (OT) at passage 1 (P1) were analyzed by exome sequencing and immunohistochemistry. All primary tumors and orthotopic tumors at passages 1 and 4 were analyzed by expression array (except NF1-MPNST-001 PT, SP-MPNST-001 OT P4, and NF1-S462 OT P4). Copy number analysis (CNA) was performed in all samples.

Mentions: We generated five MPNST orthoxenograft mouse models: two from sporadic tumors, two from independent tumors of the same NF1 patient, and one corresponding to the engraftment of the MPNST cell line S462 (Fig1 and Table1). None of the primary tumors received radiotherapy or chemotherapy prior to surgery. Human tumors (2–3 mm3) were grafted onto the sciatic nerve of nude mice following the procedure outlined in Materials and Methods.


Comprehensive establishment and characterization of orthoxenograft mouse models of malignant peripheral nerve sheath tumors for personalized medicine.

Castellsagué J, Gel B, Fernández-Rodríguez J, Llatjós R, Blanco I, Benavente Y, Pérez-Sidelnikova D, García-Del Muro J, Viñals JM, Vidal A, Valdés-Mas R, Terribas E, López-Doriga A, Pujana MA, Capellá G, Puente XS, Serra E, Villanueva A, Lázaro C - EMBO Mol Med (2015)

Development of orthoxenograft mouse models of MPNSTsFive orthotopic xenograft mice models were established from four different MPNSTs and one cell line. Two of the MPNSTs come from the same NF1 patient; the other two were sporadic cases. Primary tumor (2–3 mm3) or tumor cell line (3 × 106 cells) were grafted or injected in the leg of athymic nude mice, close to the sciatic nerve. Tumors were perpetuated along several passages and subsequently expanded. Several assays were performed on tumors in early passages (histopathological analysis, gene expression profiling, genomic profiling, and drug efficacy studies). *NF1-MPNST-001 at passage 4 (P4) and all primary tumors and orthotopic tumors (OT) at passage 1 (P1) were analyzed by exome sequencing and immunohistochemistry. All primary tumors and orthotopic tumors at passages 1 and 4 were analyzed by expression array (except NF1-MPNST-001 PT, SP-MPNST-001 OT P4, and NF1-S462 OT P4). Copy number analysis (CNA) was performed in all samples.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492820&req=5

fig01: Development of orthoxenograft mouse models of MPNSTsFive orthotopic xenograft mice models were established from four different MPNSTs and one cell line. Two of the MPNSTs come from the same NF1 patient; the other two were sporadic cases. Primary tumor (2–3 mm3) or tumor cell line (3 × 106 cells) were grafted or injected in the leg of athymic nude mice, close to the sciatic nerve. Tumors were perpetuated along several passages and subsequently expanded. Several assays were performed on tumors in early passages (histopathological analysis, gene expression profiling, genomic profiling, and drug efficacy studies). *NF1-MPNST-001 at passage 4 (P4) and all primary tumors and orthotopic tumors (OT) at passage 1 (P1) were analyzed by exome sequencing and immunohistochemistry. All primary tumors and orthotopic tumors at passages 1 and 4 were analyzed by expression array (except NF1-MPNST-001 PT, SP-MPNST-001 OT P4, and NF1-S462 OT P4). Copy number analysis (CNA) was performed in all samples.
Mentions: We generated five MPNST orthoxenograft mouse models: two from sporadic tumors, two from independent tumors of the same NF1 patient, and one corresponding to the engraftment of the MPNST cell line S462 (Fig1 and Table1). None of the primary tumors received radiotherapy or chemotherapy prior to surgery. Human tumors (2–3 mm3) were grafted onto the sciatic nerve of nude mice following the procedure outlined in Materials and Methods.

Bottom Line: These aggressive malignancies confer poor survival, with no effective therapy available.Our work points to differences in the engraftment process of primary tumors compared with the engraftment of established cell lines.Sorafenib (a BRAF inhibitor), in combination with doxorubicin or rapamycin, was found to be the most effective treatment for reducing MPNST growth.

View Article: PubMed Central - PubMed

Affiliation: Hereditary Cancer Program, Catalan Institute of Oncology (ICO-IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain Translational Research Laboratory ICO-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.

No MeSH data available.


Related in: MedlinePlus