VEGF expression by mesenchymal stem cells contributes to angiogenesis in pancreatic carcinoma

Autor: Georgios Kallifatidis, Rainer Saffrich, D. Frommhold, Ingrid Herr, Ariane Groth, Benjamin M. Beckermann, Alexei V. Salnikov, Helmut Friess, M.W. Büchler, Mario Schubert, Peter Büchler, Jürgen Mattern, N. Giese, Wolfgang Wagner, Anja Apel, Anthony D. Ho, Anke Diehlmann, Gerhard Moldenhauer
Jazyk: angličtina
Rok vydání: 2008
Předmět:
CD31
Male
Vascular Endothelial Growth Factor A
Cancer Research
Umbilical Veins
Platelet-derived growth factor
Angiogenesis
Cellular differentiation
Cetuximab
Angiogenesis Inhibitors
Piperazines
chemistry.chemical_compound
angiogenesis
Mice
lentivirus
Cell Movement
pancreas
Cells
Cultured
Platelet-Derived Growth Factor
Neovascularization
Pathologic
Antibodies
Monoclonal
Cell Differentiation
VEGF
Bevacizumab
Vascular endothelial growth factor A
medicine.anatomical_structure
Oncology
Benzamides
Imatinib Mesylate
Stem cell
medicine.medical_specialty
Transplantation
Heterologous
Mice
Nude
Antineoplastic Agents
Biology
Antibodies
Monoclonal
Humanized
Mesenchymal Stem Cell Transplantation
MSC
Internal medicine
Spheroids
Cellular
medicine
Animals
Humans
Cell Proliferation
Epidermal Growth Factor
Mesenchymal stem cell
Mesenchymal Stem Cells
Muscle
Smooth
Fibroblasts
Actins
Pancreatic Neoplasms
Endocrinology
Pyrimidines
chemistry
Cancer research
Bone marrow
Endothelium
Vascular
Translational Therapeutics
Zdroj: British Journal of Cancer
ISSN: 1532-1827
0007-0920
Popis: Little is known about the factors that enable the mobilisation of human mesenchymal stem cells (MSC) from the bone marrow into the blood stream and their recruitment to and retention in the tumour. We found specific migration of MSC towards growth factors present in pancreatic tumours, such as PDGF, EGF, VEGF and specific inhibitors Glivec, Erbitux and Avastin interfered with migration. Within a few hours, MSC migrated into spheroids consisting of pancreatic cancer cells, fibroblasts and endothelial cells as measured by time-lapse microscopy. Supernatant from subconfluent MSC increased sprouting of HUVEC due to VEGF production by MSC itself as demonstrated by RT-PCR and ELISA. Only few MSCs were differentiated into endothelial cells in vitro, whereas in vivo differentiation was not observed. Lentiviral GFP-marked MSCs, injected in nude mice xenografted with orthotopic pancreatic tumours, preferentially migrated into the tumours as observed by FACS analysis of green fluorescent cells. By immunofluorescence and intravital microscopic studies, we found the interaction of MSC with the endothelium of blood vessels. Mesenchymal stem cells supported tumour angiogenesis in vivo, that is CD31(+) vessel density was increased after the transfer of MSC compared with siVEGF-MSC. Our data demonstrate the migration of MSC toward tumour vessels and suggest a supportive role in angiogenesis.
Databáze: OpenAIRE
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