侵袭性实体瘤动力学和形态学的多样性
Diversity of Dynamics and Morphologies of Invasive Solid Tumors
摘要：
复杂的肿瘤-宿主相互作用可显著影响进展性肿瘤的生长动力学和形态学。受限实体肿瘤的生长诱导周围微环境的机械压力和变形，这反过来影响肿瘤生长。本文推广了近年来发展起来的元胞自动机模型，用于研究异质微环境中的侵袭性肿瘤生长[Y. Jiao和S. Torquato，PLoS Comput。7，e1002314（2011）]通过引入压力的影响来测定。具体来说，我们明确地模拟由于微环境的变形及其对局部肿瘤-宿主界面不稳定性的影响而施加在生长肿瘤上的压力。研究了非侵入性增殖性生长和侵入性生长，其中单个细胞从原发性肿瘤中分离并迁移到周围微环境中。我们发现，虽然在“软”均匀微环境中生长的非侵入性肿瘤几乎形成各向同性的形状，但高压和宿主异质性都可以强烈增强恶性行为，导致肿瘤表面的手指状突起。此外，我们发现，单个侵袭性肿瘤的侵袭性细胞降解肿瘤-宿主界面的局部细胞外基质，这减少了原发性肿瘤的指状生长。我们的研究结果对癌症诊断，预后和治疗的影响进行了讨论。
英文摘要：
Complex tumor-host interactions can significantly affect the growth dynamics and morphologies of progressing neoplasms. The growth of a confined solid tumor induces mechanical pressure and deformation of the surrounding microenvironment, which in turn influences tumor growth. In this paper, we generalize a recently developed cellular automaton model for invasive tumor growth in heterogeneous microenvironments [Y. Jiao and S. Torquato, PLoS Comput. Biol. 7, e1002314 (2011)] by incorporating the effects of pressure. Specifically, we explicitly model the pressure exerted on the growing tumor due to the deformation of the microenvironment and its effect on the local tumor-host interface instability. Both noninvasive-proliferative growth and invasive growth with individual cells that detach themselves from the primary tumor and migrate into the surrounding microenvironment are investigated. We find that while noninvasive tumors growing in "soft" homogeneous microenvironments develop almost isotropic shapes, both high pressure and host heterogeneity can strongly enhance malignant behavior, leading to finger-like protrusions of the tumor surface. Moreover, we show that individual invasive cells of an invasive tumor degrade the local extracellular matrix at the tumor-host interface, which diminishes the fingering growth of the primary tumor. The implications of our results for cancer diagnosis, prognosis and therapy are discussed.
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