Journal
CANCER RESEARCH
Volume 72, Issue 24, Pages 6371-6381Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-12-0762
Keywords
-
Categories
Funding
- Fondazione CR Trieste, Trieste, Italy
- FIRB project [RBAP11Z4Z9]
- European Research Council (ERC) Advanced Grant FunSel [250124]
- Associazione Italiana per la Ricerca sul Cancro (AIRC)
- European Research Council (ERC) [250124] Funding Source: European Research Council (ERC)
Ask authors/readers for more resources
Improving tumor perfusion, thus tempering tumor-associated hypoxia, is known to impair cancer progression. Previous work from our laboratory has shown that VEGF-A165 and semaphorin 3A (Sema3A) promote vessel maturation through the recruitment of a population of circulating monocytes expressing the neuropilin-1 (Nrp1) receptor (Nrp1-expressing monocytes; NEM). Here, we define the characteristics of bone marrow NEMs and assess whether these cells might represent an exploitable tool to induce tumor vessel maturation. Gene expression signature and surface marker analysis have indicated that NEMs represent a specific subset of CD11b+ Nrp1+ Gr1- resident monocytes, distinctively recruited by Sema3A. NEMs were found to produce several factors involved in vessel maturation, including PDGFb, TGF-beta, thrombospondin-1, and CXCL10; consistently, they were chemoattractive for vascular smooth muscle cells in vitro. When directly injected into growing tumors, NEMs, isolated either from the bone marrow or from Sema3A-expressing muscles, exerted antitumor activity despite having no direct effects on the proliferation of tumor cells. NEM inoculation specifically promoted mural cell coverage of tumor vessels and decreased vascular leakiness. Tumors treated with NEMs were smaller, better perfused and less hypoxic, and had a reduced level of activation of HIF-1 alpha. We conclude that NEMs represent a novel, unique population of myeloid cells that, once inoculated into a tumor, induce tumor vessel normalization and inhibit tumor growth. Cancer Res; 72( 24); 6371-81. (c) 2012 AACR.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available