Mascheroni Pietro, López Alfonso Juan Carlos, Kalli Maria, Stylianopoulos Triantafyllos, Meyer-Hermann Michael, Hatzikirou Haralampos
Braunschweig Integrated Centre of Systems Biology and Helmholtz Center for Infectious Research, 38106 Braunschweig, Germany.
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany.
Cancers (Basel). 2019 May 24;11(5):716. doi: 10.3390/cancers11050716.
Tumor microenvironment is a critical player in glioma progression, and novel therapies for its targeting have been recently proposed. In particular, stress-alleviation strategies act on the tumor by reducing its stiffness, decreasing solid stresses and improving blood perfusion. However, these microenvironmental changes trigger chemo-mechanically induced cellular phenotypic transitions whose impact on therapy outcomes is not completely understood. In this work we analyze the effects of mechanical compression on migration and proliferation of glioma cells. We derive a mathematical model of glioma progression focusing on cellular phenotypic plasticity. Our results reveal a trade-off between tumor infiltration and cellular content as a consequence of stress-alleviation approaches. We discuss how these novel findings increase the current understanding of glioma/microenvironment interactions and can contribute to new strategies for improved therapeutic outcomes.
肿瘤微环境是胶质瘤进展中的关键因素，最近有人提出了针对它的新疗法。特别是，减轻应激策略通过降低肿瘤硬度、减少固体应力和改善血液灌注来作用于肿瘤。然而，这些微环境变化会引发化学机械诱导的细胞表型转变，其对治疗结果的影响尚未完全了解。在这项工作中，我们分析了机械压缩对胶质瘤细胞迁移和增殖的影响。我们推导了一个聚焦于细胞表型可塑性的胶质瘤进展数学模型。我们的结果揭示了减轻应激方法导致的肿瘤浸润和细胞含量之间的权衡。我们讨论了这些新发现如何增进当前对胶质瘤/微环境相互作用的理解，并有助于制定改善治疗结果的新策略。
