دورية أكاديمية

Tie2-mediated vascular remodeling by ferritin-based protein C nanoparticles confers antitumor and anti-metastatic activities

التفاصيل البيبلوغرافية
العنوان: Tie2-mediated vascular remodeling by ferritin-based protein C nanoparticles confers antitumor and anti-metastatic activities
المؤلفون: Young Sun Choi, Hyeonha Jang, Biki Gupta, Ji-Hak Jeong, Yun Ge, Chul Soon Yong, Jong Oh Kim, Jong-Sup Bae, Im-Sook Song, In-San Kim, You Mie Lee
المصدر: Journal of Hematology & Oncology, Vol 13, Iss 1, Pp 1-18 (2020)
بيانات النشر: BMC, 2020.
سنة النشر: 2020
المجموعة: LCC:Diseases of the blood and blood-forming organs
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
مصطلحات موضوعية: Antitumor immune response, EPCR, Ferritin-based protein C nanoparticles, Tie2, Vascular normalization, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: Abstract Background Conventional therapeutic approaches for tumor angiogenesis, which are primarily focused on the inhibition of active angiogenesis to starve cancerous cells, target the vascular endothelial growth factor signaling pathway. This aggravates hypoxia within the tumor core and ultimately leads to increased tumor proliferation and metastasis. To overcome this limitation, we developed nanoparticles with antiseptic activity that target tumor vascular abnormalities. Methods Ferritin-based protein C nanoparticles (PCNs), known as TFG and TFMG, were generated and tested in Lewis lung carcinoma (LLC) allograft and MMTV-PyMT spontaneous breast cancer models. Immunohistochemical analysis was performed on tumor samples to evaluate the tumor vasculature. Western blot and permeability assays were used to explore the role and mechanism of the antitumor effects of PCNs in vivo. For knocking down proteins of interest, endothelial cells were transfected with siRNAs. Statistical analysis was performed using one-way ANOVA followed by post hoc Dunnett’s multiple comparison test. Results PCNs significantly inhibited hypoxia and increased pericyte coverage, leading to the inhibition of tumor growth and metastasis, while increasing survival in LLC allograft and MMTV-PyMT spontaneous breast cancer models. The coadministration of cisplatin with PCNs induced a synergistic suppression of tumor growth by improving drug delivery as evidenced by increased blood prefusion and decreased vascular permeability. Moreover, PCNs altered the immune cell profiles within the tumor by increasing cytotoxic T cells and M1-like macrophages with antitumor activity. PCNs induced PAR-1/PAR-3 heterodimerization through EPCR occupation and PAR-1 activation, which resulted in Gα13-RhoA-mediated-Tie2 activation and stabilized vascular tight junctions via the Akt-FoxO3a signaling pathway. Conclusions Cancer treatment targeting the tumor vasculature by inducing antitumor immune responses and enhancing the delivery of a chemotherapeutic agent with PCNs resulted in tumor regression and may provide an effective therapeutic strategy.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1756-8722
Relation: http://link.springer.com/article/10.1186/s13045-020-00952-9; https://doaj.org/toc/1756-8722
DOI: 10.1186/s13045-020-00952-9
URL الوصول: https://doaj.org/article/db80f33a15cc4fada2f1b9246ca794b9
رقم الأكسشن: edsdoj.b80f33a15cc4fada2f1b9246ca794b9
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:17568722
DOI:10.1186/s13045-020-00952-9