Heightened CXCR4 and CXCL12 expression in NF1-associated neurofibromas
Neurofibromatosis type 1 (NF1) is a common autosomal dominantly inherited disorder that affects both the skin and the nervous system. NF1 occurs due to the mutations in the NF1 gene. Neurofibromas are the most common Schwann cell-based tumors in NF1 patients, which are mainly categorized into dermal and plexiform neurofibromas. Studies on different tumor types demonstrate that CXCR4 expression increases in tumor tissues and is linked to metastasis and cancer progression.
In the present study, we aimed to analyze the gene expression of CXCR4, and its ligand CXCL12, in human neurofibromas.
Eight NF1 patients aged between 5 and 37 (2 males, 6 females) were selected. The patient group comprised 1 plexiform neurofibroma, 1 pheochromocytoma, and 6 dermal neurofibromas. Following pathological examination and diagnosis, tumors were co-stained with antibodies against Schwann cell marker S100 and target molecule CXCR4. CXCR4 expression in Schwann cell-based tumors was detected at the protein level. RNA isolated from the same tumors was used for RT-PCR-based studies to measure the quantitative expression of CXCR4 and CXCL12.
CXCR4 gene expression increased 3- to 120-fold and CXCL12 gene expression increased 33- to 512-fold in all human Schwann cell-based tumors.
In order to validate the role of CXCR4 and its relationship with CXCL12 in NF1, future studies should be performed with additional tumors and different tumor types.
KeywordsNeurofibromatosis type 1 Neurofibroma Plexiform neurofibroma CXCR4 CXCL12
The authors would like to thank all families who participated in this work.
This study was supported by the Hacettepe University Scientific Research Foundation (06 01 101 021).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 10.Mo W, Chen J, Patel A, Zhang L, Chau V, Li Y, Cho W, Lim K, Xu J, Lazar AJ, Creigton CJ, Bolshakov S, McKay RM, Lev D, Le LQ, Parada LF (2013) CXCR4/CXCL12 mediate autocrine cell- cycle progression in NF1-associated malignant peripheral nerve sheath tumors. Cell 152:1077–1090CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Dombi E, Baldwin A, Marcus LJ, Fisher MJ, Weiss B, Kim AR, Whitcomb P, Martin S, Aschbacher-Smith LE, Rizvi TA, Wu J, Ershler R, Wolters P, Therrien J, Glod J, Belasco JB, Schorry E, Brofferio A, Starosta AJ, Gillespie A, Doyle AL, Ratner N, Widemann BC (2016) Activity of selumetinib in neurofibromatosis type 1–related plexiform neurofibromas. N Engl J Med 375:2550–2560CrossRefPubMedPubMedCentralGoogle Scholar