Expression of the chemokines CXCL12 and CX3CL1 and their receptors in human nerve sheath tumors

Abstract

Peripheral nerve sheath tumors are in most cases slowly growing neoplasms that can be adequately cured by surgical resection. However, facing the risk of a neurosurgical intervention and the trend of multiple relapses of nerve sheath tumors the development of additional therapy strategies seems to be favourable, and therefore substantiated knowledge of molecular and cellular mechanisms in nerve sheath tumors should be achieved. Here, we firstly describe the expression of the chemokines CXCL12 (SDF-1) and CX3CL1 (fractal-kine) and their respective receptors CXCR4, CXCR7 and CX3CR1 in different entities of human nerve sheath tumors and normal control tissues. Both ligands and their receptors are expressed in high to moderate levels on mRNA and protein level in benign and malignant nerve sheath tumors. While CXCL12 was mainly found in schwannoma cells (S100+) in situ, its receptor CXCR4 is also partly found on CD11b-positive macrophages / microglia and its alternative receptor CXCR7 is also expressed by endothelial cells and macrophages. CX3CL1 is expressed by parts of the schwannoma and endothelial cells, whereas its receptor CX3CR1 is expressed by nearly all tumor cells and macrophages, but not by endothelial cells. Taken together, we could show the presence of CXCL12 and CX3CL1 and their respective receptors in benign and malignant human nerve sheath tumors. Further investigations may show their functional role in health and disease.