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1.
Nat Immunol ; 24(11): 1813-1824, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37813965

RESUMO

Kupffer cells, the liver tissue resident macrophages, are critical in the detection and clearance of cancer cells. However, the molecular mechanisms underlying their detection and phagocytosis of cancer cells are still unclear. Using in vivo genome-wide CRISPR-Cas9 knockout screening, we found that the cell-surface transmembrane protein ERMAP expressed on various cancer cells signaled to activate phagocytosis in Kupffer cells and to control of liver metastasis. ERMAP interacted with ß-galactoside binding lectin galectin-9 expressed on the surface of Kupffer cells in a manner dependent on glycosylation. Galectin-9 formed a bridging complex with ERMAP and the transmembrane receptor dectin-2, expressed on Kupffer cells, to induce the detection and phagocytosis of cancer cells by Kupffer cells. Patients with low expression of ERMAP on tumors had more liver metastases. Thus, our study identified the ERMAP-galectin-9-dectin-2 axis as an 'eat me' signal for Kupffer cells.


Assuntos
Citofagocitose , Células de Kupffer , Humanos , Fagocitose/genética , Galectinas/genética , Galectinas/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo
2.
Biomed Pharmacother ; 95: 111-119, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28837877

RESUMO

M2 macrophages play critical roles in the progression of hepatocellular carcinoma (HCC), and they are associated with poor outcomes. TGF-ß-induced epithelial-mesenchymal transition (EMT) has been shown to be critically important to cancer cell dissemination in HCC. However, the relationship between stromal-like HCC cells and M2 macrophages formation is not clear. Here, we interrogated the molecular link between mesenchymal-like HCC cells and the formation of M2 macrophages. We demonstrated that mesenchymal-like HCC cells secrete connective tissue growth factor (CTGF) to polarized macrophages. Reciprocally, Chemokine ligand 18 (CCL18) from M2 macrophages promotes HCC progression. Furthermore, CTGF and CCL18 were increased significantly in HCC compared to adjacent normal liver tissues. In summary, our study discovered a positive feedback loop between CTGF and CCL18 in HCC metastasis. Targeting CTGF or CCL18 might provide beneficial effects for the clinical treatment of HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Quimiocinas CC/metabolismo , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/metabolismo , Macrófagos/fisiologia , Linhagem Celular Tumoral , Movimento Celular , Quimiocinas CC/genética , Fator de Crescimento do Tecido Conjuntivo/genética , Humanos
3.
Nat Commun ; 8: 15018, 2017 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-28436430

RESUMO

Transition metal oxides with a perovskite crystal structure exhibit a variety of physical properties associated with the lattice. Among these materials, strontium ruthenate (SrRuO3) displays unusually strong coupling of charge, spin and lattice degrees of freedom that can give rise to the photostriction, that is, changes in the dimensions of material due to the absorption of light. In this study, we observe a photon-induced strain as high as 1.12% in single domain SrRuO3, which we attribute to a nonequilibrium of phonons that are a result of the strong interaction between the crystalline lattice and electrons excited by light. In addition, these light-induced changes in the SrRuO3 lattice affect its electrical resistance. The observation of both photostriction and photoresistance in SrRuO3 suggests the possibility of utilizing the mechanical and optical functionalities of the material for next-generation optoelectronics, such as remote switches, light-controlled elastic micromotors, microactuators and other optomechanical systems.

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