Abstract
Purpose: The close association of lymphatic and blood vessels and their coordinated development in vivo suggest that there are parallel mechanisms regulating hemangiogenesis and lymphangiogenesis. Here, we hypothesize that inhibition of the Src tyrosine kinase, apart from anti-hemangiogenic effects, results in a suppression of lymphangiogenesis. Experimental design: The ability of the Src kinase inhibitor PP2 to block Src in isolated lymphatic endothelial cells (LECs) was analyzed by Western Blot. The effects of PP2 on LEC proliferation, migration, and sprouting were assessed by MTT, Boyden chamber, and spheroid assays, respectively. The level of VEGF-C secreted by L3.6pl pancreatic carcinoma cells was measured by ELISA. For in vivo assessment of lymphangiogenesis, Src kinase inhibitor AZM475271 was used in mouse corneal micropocket and lymphangioma models. Results: VEGF-C stimulation of isolated LECs led to an increased phosphorylation of Src kinase that was abrogated by PP2. Treatment with PP2 inhibited spheroid sprouting of LECs at even lower concentrations than suggested by the proliferation assay. Src inhibition significantly reduced the level of VEGF-C in L3.6pl supernatant. Treatment with PP2 also resulted in a significant reduction in the migratory activity of LECs. In vivo, Src inhibition reduced de novo formation of lymphangiomas and corneal neovascularization. Conclusions: Inhibition of Src kinase shows strong anti-lymphangiogenic activity in vitro and in vivo. Together with antiangiogenic effects mediated by Src inhibition, this strategy may be attractive in the treatment of lymphatic and hematogeneous metastasis of cancer.
Keywords: Lymphangiogenesis, vascular endothelial growth factor C, human lymphatic endothelial cell, Src tyrosine kinase, lymphangioma model
Current Cancer Drug Targets
Title: Src Tyrosine Kinase Inhibition Suppresses Lymphangiogenesis In Vitro and In Vivo
Volume: 10 Issue: 5
Author(s): I. Ischenko, H. Seeliger, P. Camaj, A. Kleespies, M. Guba, M.E. Eichhorn, K.-W. Jauch and C.J. Bruns
Affiliation:
Keywords: Lymphangiogenesis, vascular endothelial growth factor C, human lymphatic endothelial cell, Src tyrosine kinase, lymphangioma model
Abstract: Purpose: The close association of lymphatic and blood vessels and their coordinated development in vivo suggest that there are parallel mechanisms regulating hemangiogenesis and lymphangiogenesis. Here, we hypothesize that inhibition of the Src tyrosine kinase, apart from anti-hemangiogenic effects, results in a suppression of lymphangiogenesis. Experimental design: The ability of the Src kinase inhibitor PP2 to block Src in isolated lymphatic endothelial cells (LECs) was analyzed by Western Blot. The effects of PP2 on LEC proliferation, migration, and sprouting were assessed by MTT, Boyden chamber, and spheroid assays, respectively. The level of VEGF-C secreted by L3.6pl pancreatic carcinoma cells was measured by ELISA. For in vivo assessment of lymphangiogenesis, Src kinase inhibitor AZM475271 was used in mouse corneal micropocket and lymphangioma models. Results: VEGF-C stimulation of isolated LECs led to an increased phosphorylation of Src kinase that was abrogated by PP2. Treatment with PP2 inhibited spheroid sprouting of LECs at even lower concentrations than suggested by the proliferation assay. Src inhibition significantly reduced the level of VEGF-C in L3.6pl supernatant. Treatment with PP2 also resulted in a significant reduction in the migratory activity of LECs. In vivo, Src inhibition reduced de novo formation of lymphangiomas and corneal neovascularization. Conclusions: Inhibition of Src kinase shows strong anti-lymphangiogenic activity in vitro and in vivo. Together with antiangiogenic effects mediated by Src inhibition, this strategy may be attractive in the treatment of lymphatic and hematogeneous metastasis of cancer.
Export Options
About this article
Cite this article as:
Ischenko I., Seeliger H., Camaj P., Kleespies A., Guba M., Eichhorn M.E., Jauch K.-W. and Bruns C.J., Src Tyrosine Kinase Inhibition Suppresses Lymphangiogenesis In Vitro and In Vivo, Current Cancer Drug Targets 2010; 10 (5) . https://dx.doi.org/10.2174/156800910791517181
DOI https://dx.doi.org/10.2174/156800910791517181 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Innovative Cancer Drug Targets: A New Horizon in Oncology
Cancer remains one of the most challenging diseases, with its complexity and adaptability necessitating continuous research efforts into more effective and targeted therapeutic approaches. Recent years have witnessed significant progress in understanding the molecular and genetic basis of cancer, leading to the identification of novel drug targets. These include, but ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Clinical Development of Microbicides for the Prevention of HIV Infection
Current Pharmaceutical Design Stilbenes and Xanthones from Medicinal Plants as Potential Antitumor Agents
Current Bioactive Compounds Unknown Primary Squamous Cell Carcinoma of the Head and Neck
Current Cancer Therapy Reviews Recent Patents Concerning Modulators of Protein Kinase C
Recent Patents on DNA & Gene Sequences Diagnostic Usefulness of Tumor Markers in the Thyroid Cytological Samples Extracted by Fine-Needle Aspiration Biopsy
Endocrine, Metabolic & Immune Disorders - Drug Targets Particle Sorting in Microfluidic Systems
Micro and Nanosystems Colloidal Drug Delivery Systems in Vaccine Delivery
Current Drug Targets Talazoparib Loaded Solid Lipid Nanoparticles: Preparation, Characterization and Evaluation of the Therapeutic Efficacy In vitro
Current Drug Delivery Matrix Metalloproteinase Inhibitor MMI-166 Suppresses the Growth of SW1990 Human Pancreatic Cancer Cells
Current Signal Transduction Therapy Potential of Nanocarriers in Genetic Immunization
Recent Patents on Drug Delivery & Formulation The Antimitotic Potential of PARP Inhibitors, An Unexplored Therapeutic Alternative
Current Topics in Medicinal Chemistry Challenges and Opportunities for Cancer Vaccines in the Current NSCLC Clinical Scenario
Current Topics in Medicinal Chemistry The Application of lncRNAs in Cancer Treatment and Diagnosis
Recent Patents on Anti-Cancer Drug Discovery 2,3-Dichloroquinoxaline in Cross-coupling Reactions: A Single Substrate, Many Possibilities
Current Organic Chemistry Protein Kinase C as a Drug Target Implications for Drug or Diet Prevention and Treatment of Cancer
Current Drug Targets Anticancer Advances of Matrine and Its Derivatives
Current Pharmaceutical Design Lobaplatin Induces Pyroptosis in Cervical Cancer Cells via the Caspase-3/GSDME Pathway
Anti-Cancer Agents in Medicinal Chemistry The Effect of Educational Intervention Based on Health Belief Model on Beliefs Towards Human Papillomavirus Vaccination in a Sample of Iranian Female Nursing Students
Current Women`s Health Reviews Transposon-Based Engineering of Clinical-Grade T Cells for Cancer Therapy
Current Drug Therapy Molecular Targeted Approaches to Cancer Therapy and Prevention Using Chalcones
Current Cancer Drug Targets