Decrease of VEGF-A in myeloid cells attenuates glioma progression and prolongs survival in an experimental glioma model.

Background: Glioblastomas are highly vascularized tumors with a prominent infiltration of macrophages/microglia whose role in promoting glioma growth, invasion, and angiogenesis has not been fully elucidated.

Methods: The contribution of myeloid-derived vascular endothelial growth factor (VEGF) to glioma growth was analyzed in vivo in a syngeneic intracranial GL261 glioma model using a Cre/loxP system to knock out the expression of VEGF-A in CD11b + myeloid cells. Changes in angiogenesis-related gene expression profile were analyzed in mutant bone marrow-derived (BMD) macrophages in vitro.

Lack of evidence for PlGF mediating the tumor resistance after anti-angiogenic therapy in malignant gliomas.

Placenta growth factor (PlGF) is a member of vascular endothelial growth factor family which can promote cancer growth by various mechanisms. Placenta growth factor is upregulated in many neoplastic diseases and serum levels of PlGF are increased in cancer patients following anti-angiogenic therapy. However, its role in glioma growth is yet not fully elucidated.

Bone marrow chimera experiments to determine the contribution of hematopoietic stem cells to cerebral angiogenesis.

The generation of bone marrow chimera in mice is a valuable tool to study a variety of cellular processes. Donor bone marrow cells expressing reporter genes have been used to study the process of cell differentiation and the mechanisms involved in bone marrow cell recruitment. Bone marrow cells bearing genetic manipulation have been used in bone marrow chimeras to elucidate the role of molecules in different physiological and pathological settings.

Endothelial progenitor cells do not contribute to tumor endothelium in primary and metastatic tumors.

Despite extensive research, the contribution of bone-marrow-derived endothelial progenitor cells (BM-EPC) to tumor angiogenesis remains controversial. In previous publications, the extent of incorporation of BM-EPCs into the endothelial cell (EC) layer in different tumor models has been reported as significant in some studies but undetectable in others. Here, we studied the differentiation of BM-EPCs and its contribution to tumor vessels in experimental and spontaneous lung metastasis (B16 melanoma and prostate carcinoma), in an autochthonous transgenic model of prostate tumorigenesis, in orthotopically implanted lung tumors [Lewis lung carcinoma (LLC)], in heterotopic subcutaneous models (LLC and C1 prostate carcinoma) growing in green fluorescent protein (GFP)-expressing bone marrow (BM) chimeras.

Flt-1 signaling in macrophages promotes glioma growth in vivo.

Several lines of evidence indicate that Flt-1, a fms-like tyrosine kinase receptor, which binds to vascular endothelial growth factor (VEGF)-A, VEGF-B, and PlGF, is a positive regulator of angiogenesis in the context of tumor growth and metastasis. However, the molecular basis of its action is still not clear. Besides endothelial cells, Flt-1 is also expressed by other different cell types, including myeloid hematopoeitic cells (monocytes and macrophages).

Endothelial cell transplantation for gene therapy in experimental gliomas.

Objective: Malignant gliomas are prominent targets for cancer gene therapy approaches because of their poor prognosis despite all available therapies. Endothelial cells (ECs) are considered attractive vehicles for cell-based gene therapy because of their tropism to the tumor vasculature. In this study, we investigated the potential of ECs to incorporate into glioma vessels after intra-arterial or local application to establish whether ECs can be used as cellular vectors for gene therapy in gliomas.

Angiopoietin-1 promotes tumor angiogenesis in a rat glioma model.

Angiopoietins have been implicated in playing an important role in blood vessel formation, remodeling, maturation, and maintenance. However, the role of angiopoietins in tumor angiogenesis remains uncertain. In this study, expression of human angiopoietin-1 (hAng-1) and angiopoietin (hAng-2) was amplified in the rat glioma cell line GS9L by stable transfection using an inducible tet-off system.

Minor contribution of bone marrow-derived endothelial progenitors to the vascularization of murine gliomas.

Until recently, it was generally accepted that the vascularization of solid tumors occurred exclusively through the sprouting and co-option from pre-existing blood vessels. Growing evidence now suggests that bone marrow-derived endothelial progenitor cells (EP) circulate in the blood and may play an important role in the formation of new blood vessels in certain tumors. Whether endothelial progenitors participate in the vascularization of brain tumors has not yet been evaluated.