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It takes two to tango: mast cell and Schwann cell interactions in neurofibromas
David H. Viskochil
David H. Viskochil
Published December 15, 2003
Citation Information: J Clin Invest. 2003;112(12):1791-1793. https://doi.org/10.1172/JCI20503.
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Commentary

It takes two to tango: mast cell and Schwann cell interactions in neurofibromas

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Abstract

Neurofibromas are benign tumors comprised primarily of Schwann cells and fibroblasts. Mast cell infiltration is a well-known phenomenon; however, their role in tumor pathogenesis has been enigmatic. In an elegant set of experiments using cells derived from a murine model of neurofibromatosis 1 (NF1), Yang et al. dissect the molecular pathways involved in mast cell migration to neurofibromin-deficient Schwann cells. These results set the stage for rational development of therapeutics that could influence the multicellular microenvironment of neurofibromas to inhibit the development and/or progression of these tumors in human NF

Authors

David H. Viskochil

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Figure 1

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Illustration depicting the molecular pathways involved in mast cell recr...
Illustration depicting the molecular pathways involved in mast cell recruitment to neurofibromas. A neurofibromin-deficient Schwann cell (Nf1–/–) secretes five times the normal Kit ligand, which serves as a chemoattractant for mast cells expressing c-Kit. Mast cell migration is mediated by the Ras/PI3K/Rac2 signal transduction pathway, which is enhanced in Nf1+/– cells. Although not shown, endothelial cells also play a role in mast cell migration through the interaction of the endothelial cell VCAM-1 receptor and α4β1 integrin of the mast cell. Heterozygous inactivation of Nf1 promotes rapid mast cell haptotaxis specifically on α4β1 integrins in response to KitL. It is known that mast cells are activated in neurofibromas and degranulate; however it is yet to be determined if and how the presence of mast cells induces tumor progression. Figure courtesy of D. Wade Clapp, Indiana University School of Medicine. KitL, Kit ligand.

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