Neuropilin-2 promotes extravasation and metastasis by interacting with endothelial alpha 5 integrin

Cao, Ying, Hoeppner, Luke H., Bach, Steven, Guangqi, E., Guo, Yan, Wang, Enfeng, Wu, Jianmin, Cowley, Mark J., Chang, David K., Waddell, Nicola, Grimmond, Sean M., Biankin, Andrew V., Daly, Roger J., Zhang, Xiaohui and Mukhopadhyay, Debabrata (2013) Neuropilin-2 promotes extravasation and metastasis by interacting with endothelial alpha 5 integrin. Cancer Research, 73 14: 4579-4590. doi:10.1158/0008-5472.CAN-13-0529


Author Cao, Ying
Hoeppner, Luke H.
Bach, Steven
Guangqi, E.
Guo, Yan
Wang, Enfeng
Wu, Jianmin
Cowley, Mark J.
Chang, David K.
Waddell, Nicola
Grimmond, Sean M.
Biankin, Andrew V.
Daly, Roger J.
Zhang, Xiaohui
Mukhopadhyay, Debabrata
Title Neuropilin-2 promotes extravasation and metastasis by interacting with endothelial alpha 5 integrin
Formatted title
Neuropilin-2 promotes extravasation and metastasis by interacting with endothelial α5 integrin
Journal name Cancer Research   Check publisher's open access policy
ISSN 0008-5472
1538-7445
Publication date 2013-07
Year available 2013
Sub-type Article (original research)
DOI 10.1158/0008-5472.CAN-13-0529
Volume 73
Issue 14
Start page 4579
End page 4590
Total pages 12
Place of publication Philadelphia, PA, United States
Publisher American Association for Cancer Research
Collection year 2014
Language eng
Abstract Metastasis, the leading cause of cancer death, requires tumor cell intravasation, migration through the bloodstream, arrest within capillaries, and extravasation to invade distant tissues. Few mechanistic details have been reported thus far regarding the extravasation process or re-entry of circulating tumor cells at metastatic sites. Here, we show that neuropilin-2 (NRP-2), a multifunctional nonkinase receptor for semaphorins, vascular endothelial growth factor (VEGF), and other growth factors, expressed on cancer cells interacts with α5 integrin on endothelial cells to mediate vascular extravasation and metastasis in zebrafish and murine xenograft models of clear cell renal cell carcinoma (RCC) and pancreatic adenocarcinoma. In tissue from patients with RCC, NRP-2 expression is positively correlated with tumor grade and is highest in metastatic tumors. In a prospectively acquired cohort of patients with pancreatic cancer, high NRP-2 expression cosegregated with poor prognosis. Through biochemical approaches as well as Atomic Force Microscopy (AFM), we describe a unique mechanism through which NRP-2 expressed on cancer cells interacts with α5 integrin on endothelial cells to mediate vascular adhesion and extravasation. Taken together, our studies reveal a clinically significant role of NRP-2 in cancer cell extravasation and promotion of metastasis.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
 
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