AI Networking Cookbook: Practical recipes for AI-assisted network automation and development
TL;DR
The 786-0 renal cancer cell line-derived exosomes increased migration and invasion, however, they decreased the adhesion ability of the 786-0 cells.
M2 tumor-associated macrophages (M2-TAMs) have been reported to promote tumor growth through exosome-dependent mechanisms. However, the exact role of exosomes derived from M2-TAMs (M2-TAM-Exos) in lung cancer progression remains unclear. In The present study, M2-like macrophages (IL-4/IL-13-polarized THP-1-derived macrophages) were shown to release exosomes that lung cancer cells effectively internalized. These exosomes markedly enhanced the proliferation, migration, and invasion of lung cancer cells, thereby promoting malignancy. Further analyses revealed that M2-like macrophage-derived exosomes contain high levels of microRNA (miR)-491-3p. In vitro and in vivo experiments confirmed miR-491-3p as an oncogenic miR, while its inhibition markedly reduced cancer cell aggressiveness. Additional experiments demonstrated that miR-491-3p suppressed UBE2D3 expression after entering lung cancer cells. Collectively, these findings suggest a model in which M2-like macrophages deliver miR-491-3p via exosomes to downregulate UBE2D3, facilitating lung cancer progression.
OBJECTIVES This study utilized human umbilical vein endothelial cells (HUVECs) as vector cells to examine the impact of miR-21 on the vascular differentiation of Human dental pulp stem cells (hDPSCs) in recipient cells. MiR-21 was transfected into HUVECs to modulate the levels of miR-21 in exosomes and explore associated molecular signalling mechanisms. MATERIALS AND METHODS Various groups of conditioned media were prepared to culture hDPSCs based on the differential expression of miR-21 in exosomes. Subsequently, cellular proliferation, migration, adhesion, and angiogenic capabilities were assessed. Target genes of miR-21 were validated via dual luciferase assay, along with the examination of downstream signalling pathways. RESULTS Both HUVECs-exos and overexpression groups markedly enhanced the adhesion, proliferation, migration, and angiogenic abilities of hDPSCs. However, the overexpression group exhibited a more pronounced promotional effect compared to the HUVECs-exos group, while the inhibition group showed no statistically significant differences. The dual-luciferase reporter gene assay confirmed the targeting linkage between miR-21 and JAG1, indicating that changes in miR-21 levels in hDPSCs impacted the expression of the JAG1/NOTCH1/VEGF signalling pathway. CONCLUSION HUVEC-derived exosomes with elevated miR-21 levels promote adhesion, proliferation, migration and in vitro capillary-like tube formation in hDPSCs. MiR-21 modulates hDPSCs' in vitro angiogenic phenotypes via targeting JAG1 and subsequently activating the JAG1/NOTCH1/VEGF signalling pathway.
Background Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer with an immunosuppressive microenvironment. Although CD93 promotes angiogenesis in tumor endothelial cells, its role in HNSCC tumor cells and the impact of CD93-mediated regulation of tumor cells on the tumor microenvironment are unclear. This study investigates whether CD93 promotes the malignant progression of HNSCC by enhancing tumor cell malignancy and contributing to macrophage-associated and angiogenic remodeling of the tumor microenvironment, elucidating the underlying mechanisms. Methods Bioinformatics analyses assessed CD93 expression, clinical relevance, immune infiltration, and signaling pathways in HNSCC. CD93 expression was validated in clinical specimens and cell lines. CD93 knockdown and overexpression models were used to examine invasion, migration, proliferation, and epithelial–mesenchymal transition (EMT). Conditioned media from CD93-modulated tumor cells were applied to THP-1-derived macrophages and HUVECs to assess macrophage-associated markers and endothelial tube formation. Wnt/β-catenin signaling was pharmacologically activated or inhibited. Xenograft growth and macrophage depletion were evaluated in BALB/c nude mice. Protein–protein docking was used to explore predicted spatial compatibility between CD93 and receptor-proximal Wnt pathway components. Results CD93 was upregulated in HNSCC and associated with poor prognosis and an immunosuppressive, pro-angiogenic TME. CD93 knockdown inhibited invasion, migration, proliferation, EMT-associated changes, CD206 expression, changes in macrophage-associated markers, and endothelial tube formation, whereas CD93 overexpression produced opposite effects. CD93 expression was associated with Wnt/β-catenin activation; CHIR99021 reversed the effects of CD93 knockdown, whereas XAV939 attenuated changes induced by CD93 overexpression. In vivo, CD93 knockdown suppressed xenograft growth, proliferation, angiogenesis, EMT-associated changes, CD206-positive macrophage-associated signals, and β-catenin expression. Clodronate liposome-mediated macrophage depletion reduced HSC3-shNC tumor growth and narrowed the difference between HSC3-shNC and HSC3-shCD93 tumors. Docking analysis indicated that CD93 showed the most favorable predicted spatial compatibility with LRP6 E1E2 among the tested Wnt receptor-related components. Conclusion CD93 may promote HNSCC progression by enhancing tumor-cell aggressiveness and tumor microenvironment remodeling, at least partly through Wnt/β-catenin-related signaling. Docking analysis provides a preliminary structural hypothesis for a potential CD93–LRP6 E1E2 spatial association. CD93 may represent a prognostic biomarker and candidate therapeutic target in HNSCC.
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