Molecular crosstalk between tumour and brain parenchyma instructs histopathological features in glioblastoma

• DOI: 10.18632/oncotarget.7454
• Publication Date: 2016-03-26T03:13:53Z
• Authors: Sébastien Bougnaud; Anna Golebiewska; Anaïs Oudin; Olivier Keunen; Patrick N. Harter; Lisa Mäder; Francisco Azuaje; Sabrina Fritah; Daniel Stieber; Tony Kaoma; Laurent Vallar; Nicolaas H.C. Brons; Thomas Daubon; Hrvoje Miletic; Terje Sundstrøm; Christel Herold-M...; Michel Mittelbronn; Rolf Bjerkvig; Simone P. Niclou
• Keywords: Transdifferentiation; Parenchyma; Desmoplasia; Crosstalk; Spheroid

The histopathological and molecular heterogeneity of glioblastomas represents a major obstacle for effective therapies. Glioblastomas do not develop autonomously, but evolve in unique environment that adapts to the growing tumour mass contributes malignancy these neoplasms. Here, we show patient-derived glioblastoma xenografts generated mouse brain from organotypic spheroids reproducibly give rise three different histological phenotypes: (i) highly invasive phenotype with an apparent normal vasculature, (ii) angiogenic displaying microvascular proliferation necrosis (iii) intermediate combining features invasion vessel abnormalities. These phenotypic differences were visible during early phases development suggesting instructive role cells on parenchyma. Conversely, found tumour-instructed stromal differentially influenced cell migration vitro, indicating reciprocal crosstalk between neoplastic non-neoplastic cells. We did detect any transdifferentiation into endothelial Cell type-specific transcriptomic analysis revealed strong phenotype-specific conversion two types, co-evolution Integrative bioinformatic confirmed microenvironment suggested key TGFβ1 extracellular matrix proteins as interaction modules shape progression. data provide novel insight tumour-host interactions identify stroma-specific targets may play combinatorial treatment strategies against glioblastoma.