Laboratory of Neural Development and Optical Recording (NDEVOR), Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Dev Dyn. 2013 Sep;242(9):1078-93. doi: 10.1002/dvdy.24001. Epub 2013 Jul 29.
Tissue microenvironment plays key roles in regulating the progression of aggressive tumors. Tumors are uncommon in the early embryo, suggesting that embryonic tissue microenvironments are nonpermissive for tumors. Yet, the effects of embryonic tissue microenvironments on tumor cells have not been extensively studied. We have, therefore, tested the behavior of human glioblastoma multiforme (GBM) cells transplanted into a central neural tissue microenvironment in the chicken embryo.
GBM cells were cultured as spheres to enrich for GBM stem cells (GSCs) and transduced with GFP for identification. Within the proliferative embryonic neural tissue, GSC-enriched GBM cells exhibited reduced proliferation and survival, altered gene expression, and formed no tumors, in marked contrast to their aggressive behavior in vitro and tumor formation in other tissue microenvironments including the chorioallantoic membrane of the chicken embryo and the brain of adult severe combined immunodeficiency (SCID) mice. Surviving cells in the spinal neural tube exhibited tumor-atypical expression profiles of neuron-, glia-, stem cell-, and tumor-related genes.
Embryonic neural tissue provides a poor environment for GBM cell survival and tumor formation, and redirects differentiation toward a more benign phenotype. Understanding the anti-tumorigenic effects of this embryonic tissue microenvironment could provide opportunities to develop novel therapies for GBM treatment.
组织微环境在调节侵袭性肿瘤的进展中起着关键作用。在早期胚胎中肿瘤并不常见，这表明胚胎组织微环境不利于肿瘤的发生。然而，胚胎组织微环境对肿瘤细胞的影响尚未得到广泛研究。因此，我们检测了人多形性胶质母细胞瘤（GBM）细胞在鸡胚中枢神经组织微环境中的移植行为。
为了富集 GBM 干细胞（GSCs），将 GBM 细胞培养成球体，并转导 GFP 进行鉴定。在增殖性胚胎神经组织中，富含 GSCs 的 GBM 细胞增殖和存活减少，基因表达改变，且未形成肿瘤，与它们在体外的侵袭性行为以及在其他组织微环境（包括鸡胚尿囊膜和成年重度联合免疫缺陷（SCID）小鼠的大脑）中的肿瘤形成形成鲜明对比。在脊髓神经管中存活的细胞表现出肿瘤非典型的神经元、神经胶质、干细胞和肿瘤相关基因的表达谱。
胚胎神经组织不利于 GBM 细胞的存活和肿瘤形成，并将分化重新定向为更良性的表型。了解这种胚胎组织微环境的抗肿瘤作用可能为 GBM 治疗提供新的治疗机会。
