Targeting PDGF‐mediated recruitment of pericytes blocks vascular mimicry and tumor growth
Copyright policy )Targeting PDGF‐mediated recruitment of pericytes blocks vascular mimicry and tumor growth
AbstractAggressive tumor cells can adopt an endothelial cell‐like phenotype and contribute to the formation of a tumor vasculature, independent of tumor angiogenesis. This adoptive mechanism is referred to as vascular mimicry and it is associated with poor survival in cancer patients. To what extent tumor cells capable of vascular mimicry phenocopy the angiogenic cascade is still poorly explored. Here, we identify pericytes as important players in vascular mimicry. We found that pericytes are recruited by vascular mimicry‐positive tumor cells in order to facilitate sprouting and to provide structural support of the vascular‐like networks. The pericyte recruitment is mediated through platelet‐derived growth factor (PDGF)‐B. Consequently, preventing PDGF‐B signaling by blocking the PDGF receptors with either the small tyrosine kinase inhibitor imatinib or blocking antibodies inhibits vascular mimicry and tumor growth. Collectively, the current study identifies an important role for pericytes in the formation of vascular‐like structures by tumor cells. Moreover, the mechanism that controls the pericyte recruitment provides therapeutic opportunities for patients with aggressive vascular mimicry‐positive cancer types. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
- School of Pharmaceutical Sciences Switzerland
- University of Geneva Switzerland
- Amsterdam UMC, location VUmc Netherlands
- KU Leuven Belgium
- Stockholm University Sweden
Time Factors, perivascular cells, Cell Communication/drug effects, TO-MESENCHYMAL TRANSITION, Melanoma, Experimental, vessel stabilization, Cell Communication, STEM-LIKE CELLS, Cell Proliferation/drug effects, Mice, Antineoplastic Agents, Immunological, Signal Transduction/drug effects, Pathology, vasculogenic mimicry, IN-VIVO, Platelet-Derived Growth Factor, CO-OPTION, Neovascularization, Pathologic, Biological Mimicry, Original Papers, endothelial cells, Antineoplastic Agents, Immunological/pharmacology, Tumor Burden, VASCULOGENIC MIMICRY, Oncology, PRIMARY CUTANEOUS MELANOMA, Imatinib Mesylate, Imatinib Mesylate/pharmacology, Tumor Burden/drug effects, Life Sciences & Biomedicine, Platelet-Derived Growth Factor/antagonists & inhibitors/immunology/metabolism, Signal Transduction, Mice, Nude, Pathology and Forensic Medicine, 615, 3211 Oncology and carcinogenesis, Cell Line, Tumor, melanoma, cancer, BREAST-CANCER, Animals, Humans, Protein Kinase Inhibitors, Cell Proliferation, Biological Mimicry/drug effects, Science & Technology, Melanoma, Experimental/blood supply/drug therapy/metabolism/pathology, 3202 Clinical sciences, 1103 Clinical Sciences, tumor angiogenesis, Pericytes/drug effects/metabolism/pathology, ENDOTHELIAL-CELLS, Xenograft Model Antitumor Assays, Coculture Techniques, imatinib, Protein Kinase Inhibitors/pharmacology, METASTASIS, Human medicine, Pericytes, Ewing sarcoma, ANTI-ANGIOGENIC THERAPY
Time Factors, perivascular cells, Cell Communication/drug effects, TO-MESENCHYMAL TRANSITION, Melanoma, Experimental, vessel stabilization, Cell Communication, STEM-LIKE CELLS, Cell Proliferation/drug effects, Mice, Antineoplastic Agents, Immunological, Signal Transduction/drug effects, Pathology, vasculogenic mimicry, IN-VIVO, Platelet-Derived Growth Factor, CO-OPTION, Neovascularization, Pathologic, Biological Mimicry, Original Papers, endothelial cells, Antineoplastic Agents, Immunological/pharmacology, Tumor Burden, VASCULOGENIC MIMICRY, Oncology, PRIMARY CUTANEOUS MELANOMA, Imatinib Mesylate, Imatinib Mesylate/pharmacology, Tumor Burden/drug effects, Life Sciences & Biomedicine, Platelet-Derived Growth Factor/antagonists & inhibitors/immunology/metabolism, Signal Transduction, Mice, Nude, Pathology and Forensic Medicine, 615, 3211 Oncology and carcinogenesis, Cell Line, Tumor, melanoma, cancer, BREAST-CANCER, Animals, Humans, Protein Kinase Inhibitors, Cell Proliferation, Biological Mimicry/drug effects, Science & Technology, Melanoma, Experimental/blood supply/drug therapy/metabolism/pathology, 3202 Clinical sciences, 1103 Clinical Sciences, tumor angiogenesis, Pericytes/drug effects/metabolism/pathology, ENDOTHELIAL-CELLS, Xenograft Model Antitumor Assays, Coculture Techniques, imatinib, Protein Kinase Inhibitors/pharmacology, METASTASIS, Human medicine, Pericytes, Ewing sarcoma, ANTI-ANGIOGENIC THERAPY
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