Collagen Linearization within Tumors.
Collagen Linearization within Tumors.
复制标题
肿瘤内的胶原线性化。
DOI：
10.1158/0008-5472.can-21-2939
复制
发表时间：
2021-11-15
期刊：
影响因子：
11.2
通讯作者：
中科院分区：
文献类型：
--
作者：
现在充分认识到，原发性肿瘤周围的肿瘤微环境（TME）影响肿瘤生长、进展（侵袭和迁移）和对治疗的反应。广义上讲，TME由细胞（免疫细胞、活化的成纤维细胞、脂肪细胞、内皮细胞）、无细胞细胞的细胞外基质（ECM）和细胞因子或生长因子组成，其中一些与ECM蛋白结合或栓系。所有这些隔室在肿瘤发展和进展期间经历显著变化。特别是ECM的变化可以显著影响癌症生物学。这刺激了直接逆转或预防TME ECM中促进癌症进展的结构变化的疗法的发展。但要做到这一点，以合理的方式，我们需要了解肿瘤ECM的结构变化如何产生，重塑，以及促进肿瘤细胞侵袭和迁移的功能，从而引起转移性疾病，这是癌症相关死亡的主要原因。在这一期的《癌症研究》中，Janjanam及其同事表明，肿瘤中WISP 1/WISP 2的比例对ECM胶原纤维线性化至关重要，对转移也很重要。WISP 2直接结合ECM胶原，并可抑制WISP 1介导的胶原线性化。这些新的结果提供了一种新的方法，通过阻止或逆转胶原线性化来靶向肿瘤中改变的胶原ECM。
It is now well appreciated that the tumor microenvironment (TME) surrounding primary tumors impacts tumor growth, progression (invasion and migration), and response to therapy. Broadly speaking, the TME is composed of cells (immune cells, activated fibroblasts, adipocytes, endothelial cells), acellular extracellular matrix (ECM), and cytokines or growth factors, some of which are bound or tethered to the ECM proteins. All these compartments undergo significant changes during tumor development and progression. Changes to the ECM, in particular, can dramatically influence cancer biology. This has stimulated the development of therapies that directly reverse or prevent the structural changes in the TME ECM that facilitate cancer progression. But to do so, in a rational manner, we need to understand how structural changes to tumor ECM arise, are remodeled, and function to facilitate tumor cell invasion and migration that give rise to metastatic disease, which is the main cause of cancer-related deaths. In this issue of Cancer Research, Janjanam and colleagues show that the ratio of WISP1/WISP2 in tumors is critical for ECM collagen fiber linearization and important for metastasis. WISP2 binds ECM collagen directly and can inhibit WISP1-mediated collagen linearization. These new results offer a new approach for targeting the altered collagen ECM in tumors by preventing or reversing collagen linearization.