Cryptic collagen elements as signaling hubs in the regulation of tumor growth and metastasis.
Cryptic collagen elements as signaling hubs in the regulation of tumor growth and metastasis.
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隐性胶原蛋白在肿瘤生长和转移调控中的信号中枢作用。
DOI：
10.1002/jcp.29752
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发表时间：
2020-12
影响因子：
5.6
通讯作者：
Brooks PC
中科院分区：
文献类型：
--
作者：
Han X;Caron JM;Brooks PC
细胞外基质的结构重塑是与肿瘤生长和转移相关的公认过程。组成肿瘤块的肿瘤细胞和基质细胞部分地通过与完整的和结构改变的基质蛋白物理相互作用而协同作用以促进恶性表型。为此，胶原蛋白代表细胞外基质的最丰富的组分，并且已知其控制组织学上不同的肿瘤类型以及基质细胞的多样性的行为。虽然已经建立了关于细胞与完整胶原蛋白的相互作用如何支配控制肿瘤进展的信号传导途径的重要分子理解，但关于与重塑胶原蛋白内的隐蔽或隐藏区域的相互作用如何选择性地改变信号传导级联，或者抑制这些隐蔽信号传导途径是否可以代表临床有效的治疗策略，知之甚少。在这里，我们回顾了新出现的证据有关的可能机制，选择性生成的隐蔽或隐藏的元素内胶原蛋白及其潜在的细胞表面受体，可能有利于信号转导。我们讨论的概念，细胞表面受体和这些隐藏的胶原蛋白元素之间的细胞通信联系，可以作为功能性信号传导枢纽，协调多个信号通路内肿瘤和基质细胞。最后，我们提供了一些例子来帮助说明直接靶向这些独特的隐蔽信号中枢可能导致开发更有效的治疗策略来控制肿瘤生长和转移的可能性。
Structural remodeling of the extracellular matrix is a well-established process associated with tumor growth and metastasis. Tumor and stromal cells that compose the tumor mass function cooperatively to promote the malignant phenotype in part by physically interacting with intact and structurally altered matrix proteins. To this end, collagen represents the most abundant component of the extracellular matrix and is known to control the behavior of histologically distinct tumor types as well as a diversity of stromal cells. While a significant molecular understanding has been established concerning how cellular interactions with intact collagen governs signaling pathways that control tumor progression, considerably less is known concerning how interactions with cryptic or hidden regions within remodeled collagen may selectively alter signaling cascades, or whether inhibition of these cryptic signaling pathways may represent clinically effective therapeutic strategies. Here, we review the emerging evidence concerning the possible mechanisms for the selective generation of cryptic or hidden elements within collagen and their potential cell surface receptors that may facilitate signal transduction. We discuss the concept that cellular communication links between cell surface receptors and these cryptic collagen elements may serve as functional signaling hubs that coordinate multiple signaling pathways operating within both tumor and stromal cells. Finally, we provide examples to help illustrate the possibility that direct targeting of these unique cryptic signaling hubs may lead to the development of more effective therapeutic strategies to control tumor growth and metastasis.
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