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Neuropilin-2 expression in cancer
Adrian M Jubb1, Susan M Sa, Navneet Ratti
1Department of Pathology, Genentech Inc., South San Francisco, CA 94080, USA. adrianj@gene.com
Histopathology
|March 6, 2012
Summary
Neuropilin-2 is expressed in blood and lymphatic vessels across various cancers. Its tumor cell expression varies, impacting anti-neuropilin-2 therapy effectiveness in lung, breast, and colorectal cancers.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Metastasis
Background:
- Neuropilin-2 (NRP2) acts as a coreceptor for vascular endothelial growth factor (VEGF) family members.
- Blocking NRP2 has shown potential in suppressing lymphogenous metastasis in preclinical cancer models.
Purpose of the Study:
- To validate an in situ protocol for evaluating neuropilin-2 protein expression.
- To compare in situ protein expression with in situ hybridization, western blotting, and mRNA levels.
Main Methods:
- Immunohistochemistry was performed on normal human tissues and 79 primary non-small-cell lung carcinomas, 65 primary breast carcinomas, 79 primary colorectal cancers, and 52 metastases.
- Neuropilin-2 expression was also assessed in 55 primary and 9 secondary malignant melanomas using in situ hybridization.
Main Results:
- Neuropilin-2 expression was detected in the vasculature of all normal and malignant tissues examined.
- Tumor cell expression of neuropilin-2 was observed in 32% of non-small-cell lung cancers, 15% of breast cancers, and 22% of colorectal cancers.
- In malignant melanomas, 85% of primary tumors showed tumor cell expression of neuropilin-2.
Conclusions:
- Anti-neuropilin-2 therapies are likely to primarily target the vasculature in most lung, breast, and colorectal cancers.
- These findings aid in pharmacokinetic and tolerability assessments for anti-neuropilin-2 therapies.
- The results help guide the optimal clinical setting for evaluating anti-neuropilin-2 drug activity.
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