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. Although a significant molecular understanding has been established concerning how cellular interactions with intact collagen govern 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.

中文翻译：

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隐性胶原蛋白元素作为调节肿瘤生长和转移的信号枢纽。

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。组成肿瘤块的肿瘤和基质细胞协同作用以促进恶性表型，部分是通过与完整和结构改变的基质蛋白物理相互作用。为此，胶原蛋白代表了细胞外基质中最丰富的成分，并且已知可以控制组织学上不同的肿瘤类型以及多种基质细胞的行为。尽管关于细胞与完整胶原蛋白的相互作用如何控制控制肿瘤进展的信号通路已经建立了重要的分子理解，关于与重塑胶原内的隐蔽或隐藏区域的相互作用如何选择性地改变信号级联，或者这些隐蔽信号通路的抑制是否可能代表临床有效的治疗策略，我们知之甚少。在这里，我们回顾了有关在胶原蛋白及其可能促进信号转导的潜在细胞表面受体中选择性生成神秘或隐藏元素的可能机制的新证据。我们讨论的概念是，细胞表面受体和这些神秘的胶原蛋白元素之间的细胞通讯联系可以作为功能性信号传导枢纽，协调在肿瘤和基质细胞内运行的多个信号通路。最后，