Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Division of Plastic and Reconstructive Surgery, and.
Department of Surgery, Stanford University School of Medicine, Stanford, California, USA.
JCI Insight. 2018 Sep 20;3(18). doi: 10.1172/jci.insight.99911.
The stroma in solid tumors contains a variety of cellular phenotypes and signaling pathways associated with wound healing, leading to the concept that a tumor behaves as a wound that does not heal. Similarities between tumors and healing wounds include fibroblast recruitment and activation, extracellular matrix (ECM) component deposition, infiltration of immune cells, neovascularization, and cellular lineage plasticity. However, unlike a wound that heals, the edges of a tumor are constantly expanding. Cell migration occurs both inward and outward as the tumor proliferates and invades adjacent tissues, often disregarding organ boundaries. The focus of our review is cancer associated fibroblast (CAF) cellular heterogeneity and plasticity and the acellular matrix components that accompany these cells. We explore how similarities and differences between healing wounds and tumor stroma continue to evolve as research progresses, shedding light on possible therapeutic targets that can result in innovative stromal-based treatments for cancer.
实体瘤的基质包含多种与创伤愈合相关的细胞表型和信号通路，这导致了肿瘤表现为一种无法愈合的创伤的概念。肿瘤和愈合伤口之间存在相似性，包括成纤维细胞的募集和激活、细胞外基质（ECM）成分的沉积、免疫细胞的浸润、新生血管形成和细胞谱系可塑性。然而，与愈合的伤口不同，肿瘤的边缘在不断扩大。随着肿瘤的增殖和侵袭邻近组织，细胞迁移向内和向外发生，通常无视器官边界。我们的综述重点是癌症相关成纤维细胞（CAF）的细胞异质性和可塑性以及伴随这些细胞的无细胞基质成分。我们探讨了随着研究的进展，愈合伤口和肿瘤基质之间的相似性和差异如何继续演变，这为可能的治疗靶点提供了启示，这些靶点可能导致创新的基于基质的癌症治疗方法。
