VEGF121 and VEGF165 differentially promote vessel maturation and tumor growth in mice and humans

Autor: M Kazemi, A Carrer, S Moimas, L Zandonà, R Bussani, B Casagranda, S Palmisano, P Prelazzi, M Giacca, L Zentilin, N De Manzini, S Zacchigna
Přispěvatelé: Kazemi, M, Carrer, A, Moimas, S, Zandonà, L, Bussani, R, Casagranda, B, Palmisano, S, Prelazzi, P, Giacca, M, Zentilin, L, De Manzini, N, Zacchigna, S
Rok vydání: 2016
Předmět:
Vascular Endothelial Growth Factor A
0301 basic medicine
Cancer Research
Pathology
medicine.medical_treatment
Melanoma
Experimental
Mice
chemistry.chemical_compound
0302 clinical medicine
Neoplasms
Protein Isoforms
Hypoxia
Melanoma
Regulation of gene expression
Tumor
Neovascularization
Pathologic
growth factor
tumor angiogenesis
human cancer
VEGF165 and VEGF121
Dependovirus
Immunohistochemistry
Tumor Burden
Gene Expression Regulation
Neoplastic
Vascular endothelial growth factor
Vascular endothelial growth factor A
Lymphatic Metastasis
030220 oncology & carcinogenesis
Molecular Medicine
Gene isoform
medicine.medical_specialty
Genetic Vectors
Biology
Cell Line
Experimental
03 medical and health sciences
Cell Line
Tumor
medicine
Animals
Humans
Alternative Splicing
Disease Models
Animal
Molecular Biology
Neovascularization
Pathologic
Neoplastic
Animal
Growth factor
Alternative splicing
medicine.disease
030104 developmental biology
HIF1A
Gene Expression Regulation
chemistry
Disease Models
Cancer research
tumor angiogenesi
Zdroj: Cancer Gene Therapy. 23:125-132
ISSN: 1476-5500
0929-1903
DOI: 10.1038/cgt.2016.12
Popis: Tumor angiogenesis depends on the vascular endothelial growth factor (VEGF), which exists in multiple splicing isoforms, including the most abundant VEGF165 and VEGF121. We have previously shown that the differential capacity of these two VEGF isoforms to bind Neuropilin-1 accounts for their diverse ability to recruit Nrp1-expressing monocytes (NEMs), resulting in a different arteriogenic potential. Here we measure the expression of VEGF165 and VEGF121 in human cancer and their influence on tumor growth and vascularization. We measured the expression levels of VEGF165 and VEGF121 in human colorectal cancer and found that VEGF121 was more expressed than VEGF165, particularly in patients with extensive lymph node infiltration. Overexpressing either VEGF165 or VEGF121 in a cancer mouse model, we observed that the former decreased, whereas the latter increased tumor growth. In both clinical and experimental tumors, VEGF165 expression resulted in the recruitment of NEMs, paralleled by maturation of the tumor vascular network. Finally, hypoxia induced a shift toward the VEGF165 isoform in the central core of human cancers, as well as in various types of cultured cells. These results demonstrate that the two VEGF splicing isoforms are differentially expressed in colorectal cancers, exerting opposite effects on tumor growth and vessel maturation.Cancer Gene Therapy advance online publication, 1 April 2016; doi:10.1038/cgt.2016.12.
Databáze: OpenAIRE
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