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As a key step of tumor lymphatic metastasis, lymphangiogenesis is regulated by VEGFC‐VEGFR3 signaling pathway mediated by immune cells, mainly macrophages, in the tumor microenvironment. However, little is known whether tumor associated neutrophils are involved in lymphangiogenesis. Here, it is found that TANs infiltration is increased in LN‐metastatic BCa and is associated with poor prognosis. Neutrophil depletion results in significant reduction in popliteal LN metastasis and lymphangiogenesis. Mechanistically, transcription factor ETV4 enhances BCa cells‐derived CXCL1/8 to recruit TANs, leading to the increase of VEGFA and MMP9 from TANs, and then facilitating lymphangiogenesis and LN metastasis of BCa. Moreover, phosphorylation of ETV4 at tyrosine 392 by tyrosine kinase PTK6 increases nuclear translocation of ETV4 and is essential for its function in BCa. Overall, the findings reveal a novel mechanism of how tumor cells regulate TANs‐induced lymphangiogenesis and LN metastasis and identify ETV4 as a therapeutic target of LN metastasis in BCa. [ABSTRACT FROM AUTHOR]

ETV4 Mediated Tumor-Associated Neutrophil Infiltration Facilitates Lymphangiogenesis and Lymphatic Metastasis of Bladder Cancer (Adv. Sci. 11/2023) B Tumor-Associated Neutrophil b In article number 2205613, Xu Chen, Tianxin Lin, and co-workers reveal a novel mechanism of tumor-associated neutrophil (TANs) in lymph node (LN)-metastatic bladder cancer. ETS variant transcription factor (ETV4) enhances bladder cancer (BCa) cells-derived chemokine C-X-C motif ligand (CXCL)1/8 to recruit TANs, leading to the increase of vascular endothelial growth factor A (VEGFA) and matrix metalloproteinase-9 (MMP9), and then facilitating lymphangiogenesis and LN metastasis of bladder cancer. [Extracted from the article]

Fabrication of versatile hydrogels in a facile and effective manner represents a pivotal challenge in the field of biomaterials. Herein, a novel strategy is presented for preparing on‐demand degradable hydrogels with multilevel responsiveness. By employing selenol‐dichlorotetrazine nucleophilic aromatic substitution (SNAr) to synthesize hydrogels under mild conditions in a buffer solution, the necessity of additives or posttreatments can be obviated. The nucleophilic and redox reactions between selenol and tetrazine culminate in the formation of three degradable chemical bonds—diselenide, aryl selenide, and dearomatized selenide—in a single, expeditious step. The resultant hydrogel manifests exceptional adaptability to intricate environments in conjunction with self‐healing and on‐demand degradation properties. Furthermore, the resulting material demonstrated light‐triggered antibacterial activity. Animal studies further underscore the potential of integrating metformin into Se‐Tz hydrogels under green light irradiation, as it effectively stimulates angiogenesis and collagen deposition, thereby fostering efficient wound healing. In comparison to previously documented hydrogels, Se‐Tz hydrogels exhibit controlled degradation and drug release, outstanding antibacterial activity, mechanical robustness, and bioactivity, all without the need for costly and intricate preparation procedures. These findings underscore Se‐Tz hydrogels as a safe and effective therapeutic option for diabetic wound dressings. [ABSTRACT FROM AUTHOR]