Parallels between Nerve Scar Formation and Neurofibroma Development: The Contributions of Fibroblasts
Abstract
The tumor predisposition von Recklinghausen s Neurofibromatosis type I (NF1) is one of the most common genetic disorders of the nervous system, affecting 1 in 3000 individuals. Cutaneous and plexiform neurofibromas, as well as malignant peripheral nerve sheath tumors are serious complications of NF1. Neurofibromas are complex peripheral nerve tumors and composed mainly of abnormal local cells including schwann cells, nerves, endothelial cells, fibroblasts, and a large number of infiltrating mast cells. Currently, little is known about the mechanisms mediating the initiation and progression of these tumors, or the identity of the specific cell type that gives rise to neurofibromas. Recent work in our laboratory has identified the developmental cells of origin for dermal and plexiform neurofibroma and generated novel mouse models for these complex NF1-associated tumors. These studies also provide evidence that additional signals from the tumor microenvironment play essential roles in neurofibroma formation. In the present application, we propose to elucidate the contributions of fibroblasts to the pathogenesis of neurofibroma. We put forward plans to define the cellular interactions between the neoplastic schwann cells and the fibroblasts in the tumor microenvironment, and we propose to develop novel therapy aimed at delaying or preventing neurofibroma formation in NF1 patients. These research plans are novel because we have uncovered unique paracrine interactions between the neoplastic cells (the schwann cells) and its microenvironment, including the fibroblasts, that are required for tumor formation, which could lead directly to new and potentially effective therapeutics for NF1, where none exist today. In addition, while focused on neurofibroma, this work raises the exciting possibility that the surrounding non-neoplastic cells in the tumor environment may also impact the growth of other tumor types. An increased understanding of the role of non-neoplastic tumor-associated cells may lead to new directions for cancer therapy and prevention.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1610089
Entities
People
- Lu Q Le
Organizations
- United States Army
- University of Texas Southwestern Medical Center