Department of Surgery, University of South Florida Morsani College of Medicine, Tampa, FL, USA.
Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
Adv Exp Med Biol. 2020;1224:79-85. doi: 10.1007/978-3-030-35723-8_6.
Tumors have long been compared to chronic wounds that do not heal, since they share many of the same molecular and cellular processes. In normal wounds, healing processes lead to restoration of cellular architecture, while in malignant tumors, these healing processes become dysregulated and contribute to growth and invasion of neoplastic cells into the surrounding tissues. Fibrocytes are fibroblast-like cells that differentiate from bone marrow-derived CD14 circulating monocytes and aid wound healing. Although most monocytes will differentiate into macrophages after extravasating into a tissue, signals present in a wound environment can cause some monocytes to differentiate into fibrocytes. The fibrocytes secrete matrix proteins and inflammatory cytokines, activate local fibroblasts to proliferate and increase extracellular matrix production, and promote angiogenesis, and because fibrocytes are contractile, they also help wound contraction. There is now emerging evidence that fibrocytes are present in the tumor microenvironment, attracted by the chronic tissue damage and cytokines from both cancer cells and other immune cells. Fibrocytes may aid in the survival and spread of neoplastic cells, so these wound-healing cells may be a promising target for anticancer research in future studies.
肿瘤长期以来一直被比作无法愈合的慢性伤口,因为它们具有许多相同的分子和细胞过程。在正常伤口中,愈合过程导致细胞结构的恢复,而在恶性肿瘤中,这些愈合过程失调,导致肿瘤细胞生长和侵入周围组织。纤维细胞是成纤维细胞样细胞,它们从骨髓来源的 CD14 循环单核细胞分化而来,有助于伤口愈合。尽管大多数单核细胞在渗出到组织后会分化为巨噬细胞,但伤口环境中的信号可以导致一些单核细胞分化为纤维细胞。纤维细胞分泌基质蛋白和炎症细胞因子,激活局部成纤维细胞增殖并增加细胞外基质的产生,促进血管生成,并且由于纤维细胞是收缩性的,它们还有助于伤口收缩。现在有新的证据表明,纤维细胞存在于肿瘤微环境中,被慢性组织损伤和癌细胞以及其他免疫细胞产生的细胞因子所吸引。纤维细胞可能有助于肿瘤细胞的存活和扩散,因此这些伤口愈合细胞可能是未来癌症研究中一个有前途的靶点。