Neuropilin-1 Identifies a Subset of Bone Marrow Gr1- Monocytes That Can Induce Tumor Vessel Normalization and Inhibit Tumor Growth
| Autor: | Milena Sinigaglia, Serena Zacchigna, Lorena Zentilin, Miguel Mano, Mauro Giacca, Federica Maione, Alessandro Carrer, Federico Bussolino, Enrico Giraudo, Lucia Pattarini, Silvia Moimas, Guido Serini, Giulia Ruozi |
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| Přispěvatelé: | A., Carrer, Moimas, Silvia, Zacchigna, Serena, L., Pattarini, L., Zentilin, G., Ruozi, M., Mano, M., Sinigaglia, F., Maione, G., Serini, E., Giraudo, F., Bussolino, Giacca, Mauro |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Cancer Research
Pathology Angiogenesis Inhibitors genetics/metabolism/physiology Animals Bone Marrow Cells metabolism/physiology Bone Marrow Transplantation Cell Line Tumor Cell Proliferation Humans Mice Mice Inbred BALB C Mice Inbred C57BL Monocytes metabolism/physiology Neoplasms blood supply/pathology/therapy Neuropilin-1 genetics/metabolism/physiology Receptors Cell Surface genetics/metabolism/physiology Tumor Markers Biological genetics/metabolism/physiology hologic prevention /&/ control/therapy bone marrow-derived cells Inbred C57BL Monocytes Mice 0302 clinical medicine blood supply/pathology/therapy Neoplasms Neuropilin 1 Receptors heterocyclic compounds Tumor Markers Inbred BALB C Bone Marrow Transplantation Mice Inbred BALB C 0303 health sciences education.field_of_study PDGFB Tumor Neovascularization Pathologic biology tumor vessel normalization hologic metabolism/physiology Neoplasm genetics/metabolism/physiology Receptor 3. Good health medicine.anatomical_structure Oncology Integrin alpha M 030220 oncology & carcinogenesis Animals Biomarkers Tumor Bone Marrow Cells Cell Line Tumor Humans Mice Inbred C57BL Neuropilin-1 Receptors Cell Surface Cell Proliferation Angiogenesis Inhibitor medicine.medical_specialty metabolism/physiology Population Mural cell Cell Line 03 medical and health sciences medicine CXCL10 Semaphorin 3A education Neovascularization 030304 developmental biology Pathologic genetics/metabolism/physiology Tumor Marker SEMA3A genetics/metabolism/physiology genetics/metabolism/physiology Animals Bone Marrow Cell biology.protein Cancer research Bone marrow Biomarkers Inbred C57BL Monocyte |
| Zdroj: | Cancer Research |
| Popis: | 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-β, 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-1α. 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. ©2012 AACR. |
| Databáze: | OpenAIRE |
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