PDF(Pubmed)
Abstract：
The extracellular matrix (ECM) is composed of complex fibrillar proteins, proteoglycans, and macromolecules, generated by stromal, immune, and cancer cells. The components and organisation of the matrix evolves as tumours progress to invasive disease and metastasis. In many solid tumours, dense fibrotic ECM has been hypothesised to impede therapy response by limiting drug and immune cell access. Interventions to target individual components of the ECM, collectively termed the matrisome, have, however, revealed complex tumour-suppressor, tumour-promoter, and immune-modulatory functions, which have complicated clinical translation. The degree to which distinct components of the matrisome can dictate tumour phenotypes and response to therapy is the subject of intense study. A primary aim is to identify therapeutic opportunities within the matrisome, which might support a better response to existing therapies. Many matrix signatures have been developed which can predict prognosis, immune cell content, and immunotherapy responses. In this review, we will examine key components of the matrisome which have been associated with advanced tumours and therapy resistance. We have primarily focussed here on targeting matrisome components, rather than specific cell types, although several examples are described where cells of origin can dramatically affect tumour roles for matrix components. As we unravel the complex biochemical, biophysical, and intracellular transduction mechanisms associated with the ECM, numerous therapeutic opportunities will be identified to modify tumour progression and therapy response.
摘要：
细胞外基质（ECM）由复杂的纤维状蛋白组成，蛋白聚糖,和大分子，由基质产生，免疫，和癌细胞。基质的成分和组织随着肿瘤发展为侵袭性疾病和转移而演变。在许多实体瘤中，已经假设致密性纤维化ECM通过限制药物和免疫细胞的进入来阻碍治疗反应。针对ECM各个组件的干预措施，统称为婚姻，有,然而,揭示了复杂的肿瘤抑制剂，肿瘤启动子，和免疫调节功能，复杂的临床翻译。基质组的不同成分可以决定肿瘤表型和对治疗的反应的程度是深入研究的主题。一个主要目的是在母系中确定治疗机会，这可能支持对现有疗法的更好反应。已经开发了许多可以预测预后的矩阵特征，免疫细胞含量，和免疫疗法反应。在这次审查中,我们将检查与晚期肿瘤和治疗抵抗相关的关键组元。我们在这里主要关注的是针对母系成分，而不是特定的细胞类型，尽管描述了几个例子，其中起源细胞可以显着影响基质成分的肿瘤作用。当我们解开复杂的生化时，生物物理，和与ECM相关的细胞内转导机制，将确定许多治疗机会来改变肿瘤进展和治疗反应。
