背景:肿瘤中存在神经,通过轴突发生和神经发生,因其对癌症发生和发展的影响而受到越来越多的关注,癌症神经科学的新领域正在出现。最近在前列腺癌中的一项研究表明,肿瘤微环境可能通过募集表达Doublecortin(DCX)的神经祖细胞(NPC)来影响癌症进展。然而,人类乳腺肿瘤中这种细胞的存在还没有得到全面的研究。
方法:这里,我们使用成像质谱细胞法研究了患者乳腺癌基质组织中DCX表达细胞的存在。在107例乳腺癌的组织病理学图像中,对372,468个细胞进行单细胞分析,使基质室中的神经元素的空间分辨率与这些肿瘤的临床病理特征相关。并行,我们建立了一个模拟乳腺癌神经祖细胞神经支配的3D体外模型,并使用基于质谱的全局蛋白质组学研究了两种细胞在共培养中共同进化的过程.
结果:基质存在的DCX+细胞与组织学分级较高的肿瘤有关,基底样表型,以及乳腺癌患者肿瘤组织的患者生存期较短。全球蛋白质组学分析显示,共培养中乳腺癌细胞和神经祖细胞的蛋白质组景观发生了显着变化。
结论:这些结果支持神经受累在乳腺癌中起着积极作用,并需要进一步研究神经因素与肿瘤进展的相关性。
背景:这项工作得到了挪威研究委员会通过其卓越中心资助计划的支持,项目编号223250(至洛杉矶),挪威癌症协会(L.A.A.和H.V.),挪威西部地区卫生信托基金(HelseVest)(至洛杉矶),Meltzer研究基金(至H.V.)和美国国立卫生研究院(NIH)/NIGMS授予R01GM132129(至J.A.P.)。
BACKGROUND: Presence of nerves in tumours, by axonogenesis and neurogenesis, is gaining increased attention for its impact on cancer initiation and development, and the new field of cancer neuroscience is emerging. A recent study in prostate cancer suggested that the tumour microenvironment may influence cancer progression by recruitment of Doublecortin (DCX)-expressing neural progenitor cells (NPCs). However, the presence of such cells in human breast tumours has not been comprehensively explored.
METHODS: Here, we investigate the presence of DCX-expressing cells in breast cancer stromal tissue from patients using Imaging Mass Cytometry. Single-cell analysis of 372,468 cells across histopathological images of 107 breast cancers enabled spatial resolution of neural elements in the stromal compartment in correlation with clinicopathological features of these tumours. In parallel, we established a 3D in vitro model mimicking breast cancer neural progenitor-innervation and examined the two cell types as they co-evolved in co-culture by using mass spectrometry-based global proteomics.
RESULTS: Stromal presence of DCX + cells is associated with tumours of higher histological grade, a basal-like phenotype, and shorter patient survival in tumour tissue from patients with breast cancer. Global proteomics analysis revealed significant changes in the proteomic landscape of both breast cancer cells and neural progenitors in co-culture.
CONCLUSIONS: These results support that neural involvement plays an active role in breast cancer and warrants further studies on the relevance of nerve elements for tumour progression.
BACKGROUND: This work was supported by the Research Council of Norway through its Centre of Excellence funding scheme, project number 223250 (to L.A.A), the Norwegian Cancer Society (to L.A.A. and H.V.), the Regional Health Trust Western Norway (Helse Vest) (to L.A.A.), the Meltzer Research Fund (to H.V.) and the National Institutes of Health (NIH)/NIGMS grant R01 GM132129 (to J.A.P.).