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. 2009 Aug 25:9:297.
doi: 10.1186/1471-2407-9-297.

Plexin D1 is ubiquitously expressed on tumor vessels and tumor cells in solid malignancies

Ilse Roodink  1 , Kiek Verrijp, Jos Raats, William P J Leenders
Affiliations

Plexin D1 is ubiquitously expressed on tumor vessels and tumor cells in solid malignancies

Ilse Roodink et al. BMC Cancer. .

Abstract

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.

Conclusion: 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.

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Figures

Figure 1
Figure 1
PLXND1 expression in representative clinical tumor samples. Immunohistochemical analyses using a single domain antibody against PLXND1 (Magnification ×200). PLXND1 is abundantly expressed in adenocarcinoma brain metastases (A), glioblastomas multiforme (B), neuro-endocrine lung tumors (C), an ovarian adenocarcinoma (D), and prostatic urothelial cell carcinomas (E). The arrows point at PLXND1-positive vasculature. PLXND1 is absent in both tumor vasculature (arrowheads) and tumor cells in vulvar squamous cell carcinomas (F). The insets in A and B show corresponding PLXND1 mRNA in situ hybridization analyses (Magnification ×200).
Figure 2
Figure 2
PLXND1 expression in representative clinical (tumor) samples. Immunohistochemical analyses using a single domain antibody against PLXND1 (Magnification ×200). PLXND1 is expressed at high levels in primary ductal breast carcinomas (A) and corresponding lymph node metastases (B), colon adenocarcinomas (C) and corresponding liver metastases (D) and a renal cell carcinoma (E) and corresponding brain metastasis (F). The arrows point at PLXND1-expressing tumor vessels. PLXND1 is not detected in normal human cerebral cortex (G) and heart (H) tissue samples. The insets in F, G and H show corresponding PLXND1 mRNA in situ hybridization analyses (Magnification ×200).
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