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肿瘤细胞纤维胶原重塑动力学:肿瘤相关胶原特征模型。

Dynamics of Fibril Collagen Remodeling by Tumor Cells: A Model of Tumor-Associated Collagen Signatures.

机构信息

Integrated Mathematical Oncology Department, H. Lee Moffitt Cancer Center, Research Institute, Tampa, FL 33612, USA.

Cancer Biology PhD Program, University of South Florida, Tampa, FL 33612, USA.

出版信息

Cells. 2023 Nov 22;12(23):2688. doi: 10.3390/cells12232688.

Abstract

Many solid tumors are characterized by a dense extracellular matrix (ECM) composed of various ECM fibril proteins. These proteins provide structural support and a biological context for the residing cells. The reciprocal interactions between growing and migrating tumor cells and the surrounding stroma result in dynamic changes in the ECM architecture and its properties. With the use of advanced imaging techniques, several specific patterns in the collagen surrounding the breast tumor have been identified in both tumor murine models and clinical histology images. These tumor-associated collagen signatures (TACS) include loosely organized fibrils far from the tumor and fibrils aligned either parallel or perpendicular to tumor colonies. They are correlated with tumor behavior, such as benign growth or invasive migration. However, it is not fully understood how one specific fibril pattern can be dynamically remodeled to form another alignment. Here, we present a novel multi-cellular lattice-free () agent-based model of ECM that, in contrast to static histology images, can simulate dynamic changes between TACSs. This model allowed us to identify the rules of cell-ECM physical interplay and feedback that guided the emergence and transition among various TACSs.

摘要

许多实体瘤的特征是由各种细胞外基质 (ECM) 纤维蛋白组成的致密细胞外基质。这些蛋白质为驻留细胞提供结构支持和生物学环境。生长和迁移的肿瘤细胞与周围基质之间的相互作用导致 ECM 结构及其特性的动态变化。通过使用先进的成像技术,在肿瘤鼠模型和临床组织学图像中都已经确定了围绕乳腺肿瘤的胶原的几种特定模式。这些与肿瘤相关的胶原特征 (TACS) 包括远离肿瘤的松散组织纤维和与肿瘤菌落平行或垂直排列的纤维。它们与肿瘤行为相关,例如良性生长或侵袭性迁移。然而,尚不完全清楚如何动态重塑一种特定的纤维模式以形成另一种排列。在这里,我们提出了一种新的无定形基质 (ECM) 多细胞格子自由 () 基于代理的模型,与静态组织学图像相比,该模型可以模拟 TACS 之间的动态变化。该模型使我们能够确定指导各种 TACS 出现和转变的细胞-ECM 物理相互作用和反馈的规则。

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