Plexin D1 expression is induced on tumor vasculature and tumor cells: a novel target for diagnosis and therapy?
We previously reported that during mouse embryogenesis, plexin D1 (plxnD1) is expressed on neuronal and endothelial cells. Endothelial cells gradually loose plxnD1 expression during development. Here we describe, using in situ hybridization, that endothelial plxnD1 expression is regained during tumor angiogenesis in a mouse model of brain metastasis. Importantly, we found PLXND1 expression also in a number of human brain tumors, both of primary and metastatic origin. Apart from the tumor vasculature, abundant expression was also found on tumor cells. Via panning of a phage display library, we isolated two phages that carry single-domain antibodies with specific affinity towards a PLXND1-specific peptide. Immunohistochemistry with these single-domain antibodies on the same tumors that were used for in situ hybridization confirmed PLXND1 expression on the protein level. Furthermore, both these phages and the derived antibodies specifically homed to vessels in brain lesions of angiogenic melanoma in mice after i.v. injection. These results show that PLXND1 is a clinically relevant marker of tumor vasculature that can be targeted via i.v. injections.
Roodink
Ilse
I
Department of Pathology, Radboud University Nijmegen Medical Centre, The Netherlands.
Raats
Jos
J
van der Zwaag
Bert
B
Verrijp
Kiek
K
Kusters
Benno
B
van Bokhoven
Hans
H
Linkels
Marianne
M
de Waal
Robert M W
RM
Leenders
William P J
WP
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D000918:Antibody Specificity; D001435:Bacteriophages / Q000235:genetics; D001932:Brain Neoplasms / Q000098:blood supply* / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D002161:Camelids, New World; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D012313:RNA / Q000096:biosynthesis / Q000235:genetics
D000906:Antibodies; D015816:Cell Adhesion Molecules, Neuronal; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C493082:PLXND1 protein, human; C473552:Plxnd1 protein, mouse; D012313:RNA