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Tropism of the in situ growth from biopsies of childhood neuroectodermal tumors following transplantation into experimental teratoma
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
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2014 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 134, no 7, 1630-1637 p.Article in journal (Refereed) Published
Abstract [en]

Experimental teratoma induced from human pluripotent stem cells with normal karyotype can be described as a failed embryonic process and includes besides advanced organoid development also large elements of tissue with a prolonged occurrence of immature neural components. Such immature components, although benign, exhibit strong morphological resemblance with tumors of embryonic neuroectodermal origin. Here, we demonstrate that biopsy material from childhood tumors of neural embryonic origin transplanted to mature experimental teratoma can show an exclusive preference for matching tissue. Tumor specimens from five children with; Supratentorial primitive neuroectodermal tumor (sPNET); Pilocytic astrocytoma of the brainstem; Classic medulloblastoma; peripheral primitive neuroectodermal tumor (pPNET) or neuroblastoma (NB), respectively, were transplanted. Analysis of up to 120 sections of each tumor revealed an engraftment for three of the transplanted tumors: pPNET, sPNET, and NB, with a protruding growth from the latter two that were selected for detailed examination. The histology revealed a strict tropism with a non-random integration into what morphologically appeared as matched embryonic microenvironment recuperating the patient tumor histology. The findings suggest specific advantages over xenotransplantation and lead us to propose that transplantation to the human embryonic microenvironment in experimental teratoma can be a well-needed complement for preclinical in vivo studies of childhood neuroectodermal tumors. What's new? The ability to better replicate the human neoplastic niche in vivo could help improve the predictive reliability of animal models. To that end, this study shows that biopsies from childhood neuroectodermal tumors are able to engraft into specific embryonic components of human experimental teratoma. Histological examination revealed a strict tropism of a neuroblastoma as well as a supratentorial primitive neuroectodermal tumor, showing nonrandom integration into morphologically identifiable tissues. The study opens new possibilities for the analysis of growth-promoting environmental factors and for investigating novel therapies targeted to the microenvironment of childhood neuroectodermal tumors.

Place, publisher, year, edition, pages
2014. Vol. 134, no 7, 1630-1637 p.
Keyword [en]
human, biopsy, childhood, neuroectodermal tumor, in vivo, model, stem cells
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-218536DOI: 10.1002/ijc.28498ISI: 000329579500011OAI: oai:DiVA.org:uu-218536DiVA: diva2:696065
Available from: 2014-02-12 Created: 2014-02-12 Last updated: 2014-02-12Bibliographically approved

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Cedervall, Jessica
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