The Role of the Extracellular Matrix and Its Molecular and Cellular Regulators in Cancer Cell Plasticity.
The Role of the Extracellular Matrix and Its Molecular and Cellular Regulators in Cancer Cell Plasticity.
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DOI：
10.3389/fonc.2018.00431
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发表时间：
2018
影响因子：
4.7
通讯作者：
Samuel MS
中科院分区：
文献类型：
--
作者：
Poltavets V;Kochetkova M;Pitson SM;Samuel MS
微环境包括肿瘤的所有组成部分，而不是癌细胞本身。它是高度异质性的，包括细胞组分和非细胞组分，所述细胞组分包括免疫细胞、成纤维细胞、脂肪细胞和内皮细胞，所述非细胞组分是聚合蛋白和辅助分子的网状物，称为细胞外基质（ECM）。ECM提供了癌细胞存在的生物化学和生物力学背景。癌症进展取决于癌细胞穿过ECM屏障、进入循环并建立远端转移的能力。因此，癌细胞与微环境之间的沟通是肿瘤进展的一个重要方面。在确定使癌细胞能够破坏微环境的免疫成分以促进肿瘤生长和扩散的分子机制方面取得了重大进展。虽然关于肿瘤细胞如何适应ECM的变化以及它们如何影响ECM的结构和组成知之甚少，但ECM对癌症进展的重要性现在已经得到了很好的确立。可塑性是指癌细胞改变其生理特征的能力，使其能够在恶劣的微环境中生存并抵抗治疗。例子包括干性特征的获得和上皮-间充质和间充质-上皮转化。有新的证据表明，ECM的生物化学和生物力学特性影响癌细胞的可塑性，反之亦然。该领域的突出挑战仍然是确定癌细胞建立肿瘤促进ECM特征的细胞机制，并描绘ECM诱导的癌细胞可塑性的关键分子机制。在这里，我们总结了目前对癌细胞和决定ECM特征的微环境的主要基质细胞类型之间关系的理解，以及控制这种三向相互作用以调节癌细胞可塑性的关键分子途径。我们假设，这一动态系统的全面理解将需要充分利用靶向癌细胞可塑性的ECM调节剂的机会。
The microenvironment encompasses all components of a tumor other than the cancer cells themselves. It is highly heterogenous, comprising a cellular component that includes immune cells, fibroblasts, adipocytes, and endothelial cells, and a non-cellular component, which is a meshwork of polymeric proteins and accessory molecules, termed the extracellular matrix (ECM). The ECM provides both a biochemical and biomechanical context within which cancer cells exist. Cancer progression is dependent on the ability of cancer cells to traverse the ECM barrier, access the circulation and establish distal metastases. Communication between cancer cells and the microenvironment is therefore an important aspect of tumor progression. Significant progress has been made in identifying the molecular mechanisms that enable cancer cells to subvert the immune component of the microenvironment to facilitate tumor growth and spread. While much less is known about how the tumor cells adapt to changes in the ECM nor indeed how they influence ECM structure and composition, the importance of the ECM to cancer progression is now well established. Plasticity refers to the ability of cancer cells to modify their physiological characteristics, permitting them to survive hostile microenvironments and resist therapy. Examples include the acquisition of stemness characteristics and the epithelial-mesenchymal and mesenchymal-epithelial transitions. There is emerging evidence that the biochemical and biomechanical properties of the ECM influence cancer cell plasticity and vice versa. Outstanding challenges for the field remain the identification of the cellular mechanisms by which cancer cells establish tumor-promoting ECM characteristics and delineating the key molecular mechanisms underlying ECM-induced cancer cell plasticity. Here we summarize the current state of understanding about the relationships between cancer cells and the main stromal cell types of the microenvironment that determine ECM characteristics, and the key molecular pathways that govern this three-way interaction to regulate cancer cell plasticity. We postulate that a comprehensive understanding of this dynamic system will be required to fully exploit opportunities for targeting the ECM regulators of cancer cell plasticity.
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影响因子：
2.4
作者：
Bordeleau F;Chan B;Antonyak MA;Lampi MC;Cerione RA;Reinhart-King CA
通讯作者：
Reinhart-King CA
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
6
作者：
Bekes, Erin M.;Schweighofer, Bernhard;Deryugina, Elena I.
通讯作者：
Deryugina, Elena I.
影响因子：
64.8
作者：
Bhanot, P;Brink, M;Nusse, R
通讯作者：
Nusse, R
影响因子：
8.8
作者：
Aras S;Zaidi MR
通讯作者：
Zaidi MR