Angiogenesis plays a crucial role at the early stage of tumorigenesis and tumor progression. A suitable model will be useful not only for the clarification of the underlying molecular mechanisms, but also for high-throughput identification of novel anti-angiogenesis compounds. Here, we established a zebrafish model for the purpose to investigate angiogenesis and screen anti-angiogenic compounds. Glioma U87 cells expressing red fluorescent protein (RFP) were transplanted in fli:GFP transgenic zebrafish embryos where significant angiogenesis was observed. TGF-β1 enhanced glioma-induced angiogenesis, which was inhibited by JNK inhibitor SP600125 but not p38 MAPK inhibitor SB202190, ERK inhibitor PD98059, or PI3K inhibitor LY294002, indicating the important role of TGF-β1 and JNK pathways in this process. Moreover, the glioma-induced angiogenesis was associated with macrophage infiltration that was further enhanced by TGF-β1. Therefore, our zebrafish model provides a powerful in vivo tool for the investigation of tumor-induced angiogenesis, and a cost-effective system for high-throughput screening of anti-angiogenic compounds.
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http://dx.doi.org/10.1016/j.intimp.2012.12.002 | DOI Listing |
Theranostics
January 2025
Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
The cascade of events leading to tumor formation includes induction of a tumor supporting neovasculature, as a primary hallmark of cancer. Developing vasculature is difficult to evaluate but can be captured using microfluidic chip technology and patient derived cells. Herein, we established an approach to investigate the mechanisms promoting tumor vascularization and vascular targeted therapies via co-culture of cancer spheroids and endothelial cells in a three dimensional environment.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Physics "G. Occhialini", Università degli Studi di Milano-Bicocca, Piazza Della Scienza 3, 20126 Milan, Italy.
Medullary thyroid carcinoma (MTC), a rare neuroendocrine tumor comprising 3-5% of thyroid cancers, arises from calcitonin-producing parafollicular C cells. Despite aggressive behavior, surgery remains the primary curative treatment, with limited efficacy reported for radiotherapy and chemotherapy. Recent efforts have explored the pathogenetic mechanisms of MTC, identifying it as a highly vascularized neoplasm overexpressing pro-angiogenic factors.
View Article and Find Full Text PDFNPJ Biol Phys Mech
December 2024
Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering, University of Cyprus, Nicosia, Cyprus.
Solid tumors harbor a complex and dynamic microenvironment that hinders the delivery and efficacy of therapeutic interventions. In this study, we developed and utilized a hybrid, discrete-continuous mathematical model to explore the interplay between solid tumor growth, immune response, tumor-induced angiogenesis, and antiangiogenic drugs. By integrating published data with anti-angiogenic drugs, we elucidate three primary mechanisms by which anti-angiogenesis influences tumor progression and treatment outcomes: reduction in tumor growth rate by mitigating and temporally delaying angiogenesis, normalization of blood vessel structure and function, and improving immune cell extravasation and activation.
View Article and Find Full Text PDFTheranostics
January 2025
School of Pharmacy, Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, Binzhou Medical University, Yantai 264003, China.
Copper plays an important role in the regulation of PD-L1, suggesting that reducing copper levels within tumors may enhance anti-cancer immunotherapy. Tumor microenvironment responsive copper nanodeprivator (TMECN) was developed for enhancing immunotherapy of tumor via the cross-link of mercaptopolyglycol bipyridine and dimercaptosuccinic acid modifying FePt nanoalloy using the disulfide bond. Upon entering tumor cells, the disulfide bond in TMECN is cleaved by the overexpressed glutathione, exposing abundance of sulfhydryl groups.
View Article and Find Full Text PDFJ Cell Physiol
January 2025
Department of Immunology, Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania.
Treatment of osteosarcoma is hampered by tumor hypoxia and requires alternative approaches. Although the CCL2-CCR2 axis is indispensable in tumor-induced inflammation and angiogenesis, its blockade has not been effective to date. This study aimed to characterize how CCR2 inhibition affects the crosstalk of osteosarcoma cells with immune cells to better delineate tumor resistance mechanisms that help withstand such treatment.
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