PIGF and Flt-1 on the surface of macrophages induces the production of TGF-β1 by polarized tumor-associated macrophages to promote lung cancer angiogenesis
| Autor: | Shidong Xu, Xianglong Kong, Jian Zhang, Changjun He, Sainan Pang, Boxiong Ni, Bicheng Fu, Junhui Chen, Jianlong Bu, Fucheng Zhou |
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| Rok vydání: | 2021 |
| Předmět: |
Placental growth factor
Lung Neoplasms Angiogenesis Cell Survival medicine.medical_treatment Antigens Differentiation Myelomonocytic Receptors Cell Surface Flow cytometry Transforming Growth Factor beta1 Antigens CD Tumor-Associated Macrophages medicine Human Umbilical Vein Endothelial Cells Macrophage Humans Viability assay Placenta Growth Factor Pharmacology Tumor microenvironment Vascular Endothelial Growth Factor Receptor-1 medicine.diagnostic_test Neovascularization Pathologic Chemistry Antigens Differentiation Recombinant Proteins Cytokine PIGF A549 Cells Cancer research Angiogenesis Inducing Agents |
| Zdroj: | European journal of pharmacology. 912 |
| ISSN: | 1879-0712 |
| Popis: | Background The interaction between tumor cells and tumor microenvironment is a necessary condition for promoting the metastasis of malignant tumors. Methods Two different transwell culture systems were interfered with by recombinant factor placental growth factor (re-PIGF) and the re-PIGF + transforming growth factor-β1 (TGF-β1)-neutralizing antibody (anti-TGF-β1). We performed immunofluorescence, flow cytometry and enzyme linked immunosorbent assay (ELISA) to analyze the expression of PIGF, fms-like tyrosine kinase-1 (Flt-1), macrophage marker F4/80 +, macrophage M2 marker CD163+ and TGF-β1 in vitro. Meanwhile, cell viability assay and optical microscope assay were conducted to explore the cell viability and vascularization ability of human umbilical vein endothelial cells (HUVECs). Results Re-PIGF increased the expression of PIGF in A549 cells and the expression of Flt-1 in BM-Mac cells, and significantly enhanced the ability of bone marrow-derived macrophages (BM-Mac) to transform into macrophages. At the same time, re-PIGF increased the expression of cytokine TGF-β1 in A549 cells/BM-Mac transwell culture system. On the contrary, re-PIGF + anti-TGF-β1 inhibited the expression of Flt-1 in BM-Mac cells and inhibited the ability of BM-Mac cells to transform into macrophages. Finally, re-PIGF + anti-TGF-β1 reduced the cell viability and angiogenesis of HUVECs. Conclusion The surface molecule PIGF of lung cancer cells could bind to the receptor Flt-1 on the surface of macrophages, thereby increasing the production of TGF-β1, and ultimately promoting the formation of angiogenesis in lung cancer. |
| Databáze: | OpenAIRE |
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