Neuroblastoma cells injected into experimental mature teratoma reveal a tropism for embryonic loose mesenchyme
Embryonic neural tumors are responsible for a disproportionate number of cancer deaths in children. Although dramatic improvements in survival for pediatric malignancy has been achieved in previous years advancements seem to be slowing down. For the development of new enhanced therapy
and an increased understanding of the disease, pre-clinical models better capturing the neoplastic niche are essential. Tumors of early childhood present in this respect a particular challenge. Here, we explore how components of the embryonic process in stemcell induced mature teratoma can
function as an experimental in vivo microenvironment instigating the growth of injected childhood neuroblastoma (NB) cell lines. Three human NB cell lines, IMR-32, Kelly and SK-N-BE(2), were injected into mature pluripotent stem cellinduced teratoma (PSCT) and compared to xenografts of
the same cell lines. Proliferative NB cells from all lines were readily detected in both models with a typical histology of a poorly differentiated NB tumor with a variable amount of fibrovascular stroma. Uniquely in the PSCT microenvironment, NB cells were found integrated in a nonrandom
fashion. Neuroblastoma cells were never observed in areas with well-differentiated somatic tissue i.e. bone, muscle, gut or areas of other easily identifiable tissue types. Instead, the three cell lines all showed initial growth exclusively occurring in the embryonic loose mesenchymal stroma,
resulting in a histology recapitulating NB native presentation in vivo. Whether this reflects the ‘open’ nature of loose mesenchyme more easily giving space to new cells compared to other more dense tissues, the rigidity of matrix providing physical cues modulating NB characteristics,
or if embryonic loose mesenchyme may supply developmental cues that attracted or promoted the integration of NB, remains to be tested. We tentatively hypothesize that mature PSCT provide an embryonic niche well suited for in vivo studies on NB.
Document Type: Research Article
Affiliations: 1: Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden 2: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden 3: Department of Neuroscience, Karolinska Institute, Stockholm, Sweden 4: Ann & Robert H. Lurie Children's Hospital of Chicago Research Center, Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA 5: Division of Molecular Inflammation Research, University of Tromsö, Tromsö, Norway 6: Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden
Publication date: 01 January 2013
- The International Journal of Oncology provides an international forum for the publication of the latest, cutting-edge research in the broad area of oncology and cancer treatment. The journal accepts original high quality works and reviews on all aspects of oncology research including carcinogenesis, metastasis, epidemiology, chemotherapy and viral oncology. Through fair and efficient peer review, the journal is dedicated to publishing top tier research in the field, offering authors rapid publication as well as high standards of copy-editing and production. The International Journal of Oncology is published on a monthly basis in both print and early online.
- Editorial Board
- Information for Authors
- Submit a Paper
- Subscribe to this Title
- Information for Advertisers
- Terms & Conditions
- Ingenta Connect is not responsible for the content or availability of external websites
- Access Key
- Free content
- Partial Free content
- New content
- Open access content
- Partial Open access content
- Subscribed content
- Partial Subscribed content
- Free trial content