Plexin D1 is ubiquitously expressed on tumor vessels and tumor cells in solid malignancies.
BACKGROUND
Plexin D1 is expressed on both tumor-associated endothelium and malignant cells in a number of clinical brain tumors. Recently we demonstrated that Plexin D1 expression is correlated with tumor invasion level and metastasis in a human melanoma progression series. The objective of this study was to examine whether Plexin D1 might be clinically useful as a pan-tumor vessel and pan-tumor cell target in solid tumors.


METHODS
We examined Plexin D1 expression in clinical solid tumors (n = 77) of different origin, a selection of pre-malignant lesions (n = 29) and a variety of non-tumor related tissues (n = 52) by immunohistochemistry. Signals were verified in a selection of tissues via mRNA in situ hybridization.


RESULTS
Plexin D1 is abundantly expressed on both activated established tumor vasculature and malignant cells in the majority of primary and metastatic clinical tumors, as well as on macrophages and fibroblasts. Importantly, in non-tumor related tissues Plexin D1 expression is restricted to a subset of, presumably activated, fibroblasts and macrophages.


CONCLUSIONS
We demonstrate that Plexin D1 is in general ubiquitously expressed in tumor but not normal vasculature, as well as in malignant cells in a wide range of human tissues. This expression profile highlights Plexin D1 as a potentially valuable therapeutic target in clinical solid tumors, enabling simultaneous targeting of different tumor compartments.
Roodink
Ilse
I
Dept. of Pathology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. I.Roodink@pathol.umcn.nl
Verrijp
Kiek
K
Raats
Jos
J
Leenders
William P J
WP
D001808:Blood Vessels / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009369:Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism
D015816:Cell Adhesion Molecules, Neuronal; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C493082:PLXND1 protein, human
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