Semaphorin 3E expression correlates inversely with Plexin D1 during tumor progression.
Plexin D1 (PLXND1) is broadly expressed on tumor vessels and tumor cells in a number of different human tumor types. Little is known, however, about the potential functional contribution of PLXND1 expression to tumor development. Expression of semaphorin 3E (Sema3E), one of the ligands for PLXND1, has previously been correlated with invasive behavior and metastasis, suggesting that the PLXND1-Sema3E interaction may play a role in tumor progression. Here we investigated PLXND1 and Sema3E expression during tumor progression in cases of melanoma. PLXND1 was not expressed by melanocytic cells in either naevi or melanomas in situ, whereas expression increased with invasion level, according to Clark's criteria. Furthermore, 89% of the metastatic melanomas examined showed membranous PLXND1-staining of tumor cells. Surprisingly, expression of Sema3E was inversely correlated with tumor progression, with no detectable staining in melanoma metastasis. To functionally assess the effects of Sema3E expression on tumor development, we overexpressed Sema3E in a xenograft model of metastatic melanoma. Sema3E expression dramatically decreased metastatic potential. These results show that PLXND1 expression during tumor development is strongly correlated with both invasive behavior and metastasis, but exclude Sema3E as an activating ligand.
Roodink
Ilse
I
Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. I.Roodink@pathol.umcn.nl
Kats
Gürsah
G
van Kempen
Léon
L
Grunberg
Meritha
M
Maass
Cathy
C
Verrijp
Kiek
K
Raats
Jos
J
Leenders
William
W
D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D046228:Microarray Analysis; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism*; D019700:Thrombospondin 1 / Q000378:metabolism; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D015816:Cell Adhesion Molecules, Neuronal; C490607:ECM1 protein, human; D016326:Extracellular Matrix Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C493082:PLXND1 protein, human; C494123:SEMA3E protein, human; D039961:Semaphorins; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A