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Neuropilin-1 expression in cancer and development
Adrian M Jubb1, Laura A Strickland, Scot D Liu
1Department of Pathology, Genentech Inc, South San Francisco, CA 94080, USA. adrianj@gene.com
The Journal of Pathology
|October 26, 2011
Summary
Neuropilin-1 (NRP1) is crucial for tumor growth and angiogenesis. Blocking NRP1 shows promise in suppressing tumors and inhibiting blood vessel formation, validating it as an anti-cancer target.
Area of Science:
- Oncology
- Vascular Biology
- Molecular Biology
Background:
- Neuropilin-1 (NRP1) acts as a co-receptor for vascular endothelial growth factor (VEGF).
- Preclinical studies indicate that blocking NRP1 can inhibit tumor growth by suppressing angiogenesis and tumor cell proliferation.
- A humanized monoclonal antibody targeting NRP1 is under clinical investigation for cancer therapy.
Purpose of the Study:
- To systematically characterize the in situ expression of NRP1 in human cancers and during mammalian development.
- To validate NRP1 as a therapeutic target for anti-angiogenesis and direct anti-tumor effects.
Main Methods:
- Generated and validated a monoclonal antibody for human NRP1 using immunohistochemistry, western blotting, immunofluorescence, and in situ hybridization.
- Assessed NRP1 expression in 65 primary breast, 95 colorectal, and 90 lung carcinomas, plus 59 metastases and 16 xenografts.
- Evaluated NRP1 in mouse embryos and a postnatal mouse trachea angiogenesis model.
Main Results:
- NRP1 immunoreactivity was detected in vessels of normal tissues adjacent to tumors and in 98-100% of all evaluated carcinomas.
- Tumor cell expression of NRP1 was observed in 36% of lung and 6% of breast carcinomas, but not in colorectal adenocarcinomas.
- In a mouse model, NRP1 blockade led to defective angiogenesis, mirroring anti-VEGF treatment effects.
Conclusions:
- NRP1 is widely expressed in tumor vasculature and, in a subset of cancers, on tumor cells, confirming its role in both angiogenesis and direct tumor cell targeting.
- NRP1 blockade effectively inhibits angiogenesis, supporting its validation as an anti-angiogenic target in malignancy.
- The study confirms NRP1's role in physiological, VEGF-mediated angiogenesis and its potential as a direct anti-tumor target in specific cancer types.
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