A narrative review of the role of fibroblasts in the growth and development of neurogenic tumors

Neurogenic tumors, a group of tumors arising from neurogenic elements, could theoretically appear in every region of human bodies wherever nerves exist. Patients with these tumors suffer from both physical and psychological problems. However, as a relatively rare tumor type, therapies are relatively scarce for these tumors due to the limited understanding of the underlying mechanisms. Recently, a tailored tumor microenvironment containing multiple types of nonneoplastic cells has been considered to play an essential role in tumor survival, growth, and metastasis. Fibroblasts are a crucial constituent of the tumor microenvironment and have been found to promote tumor growth via multiple mechanisms. However, the understanding of the pivotal role of fibroblasts in the tumorigenesis and development of the neurogenic tumors is still incomplete, and studies in this area show differences in rates of progression among different neurogenic tumor subtypes. Nevertheless, all these neural crest-originated neoplasms show some similarities in the tumor microenvironment, indicating that studies of one subtype of neurogenic tumor might assist in clarifying the underlying mechanisms of other subtypes. This review aims to provide current studies showing the impacts of fibroblasts on major benign/malignant subtypes of neurogenic tumors, including neurofibromatosis type 1, neuroblastomas, pheochromocytomas, and malignant peripheral nerve sheath tumors. Multiple related mechanisms such as the fibroblasts regulating the tumor inflammation, angiogenesis, metabolism, and microenvironment establishment have been studied up to present. Consistently, we focus on how studies on various subtypes of these neurogenic tumors contribute to the establishment of potential future directions for further studies in this area. Clarifying the underlying mechanisms by which fibroblasts promote the growth and metastasis of neurogenic tumors will indicate new therapeutic targets for further clinical treatment.