Overexpression of CXCL16 and its receptor CXCR6/Bonzo promotes growth of human schwannomas.
Chemokines and their receptors play a decisive role in tumor progression and metastasis. Here, we describe the expression of the CXCL16-CXCR6-system in human schwannomas of different localization and in malignant peripheral nerve sheath tumors. The transmembrane chemokine CXCL16 and its receptor CXCR6/Bonzo were overexpressed on the mRNA and protein levels in all tumor samples investigated as compared with normal peripheral or 8th cranial nerve tissues. Chromogenic immunostaining and confocal laser microscopy revealed that CXCL16 and CXCR6 were localized mainly on S-100 positive schwannoma cells. Cultured schwannoma cells responded to CXCL16-stimulation by phosphorylation of kinases p42/44 (Erk 2/1) that could be inhibited by the MEK1/2-inhibitor U0126 indicating an involvement of the mitogen-activated protein kinase signal transduction pathway. As a biological response, CXCL16 increased proliferation and induced migration of schwannomas. Hence, CXCL16 appears to be a novel growth factor for schwannomas of different localization.
Held-Feindt
Janka
J
Department of Neurosurgery, University Medical Center Schleswig-Holstein, Kiel, Germany. held-feindtj@nch.uni-kiel.de
Rehmke
Brigitte
B
Mentlein
Rolf
R
Hattermann
Kirsten
K
Knerlich
Friederike
F
Hugo
Heinz-Hermann
HH
Ludwig
Andreas
A
Mehdorn
H Maximilian
HM
D002455:Cell Division; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D009442:Neurilemmoma / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000235:genetics*; D051116:Receptors, Scavenger / Q000235:genetics*; D011991:Receptors, Virus / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013120:Spinal Cord Neoplasms / Q000235:genetics / Q000473:pathology
C423727:CXCL16 protein, human; C106330:CXCR6 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D051116:Receptors, Scavenger; D011991:Receptors, Virus