Lung Cancer Cell-Derived Secretome Mediates Paraneoplastic Inflammation and Fibrosis in Kidney in Mice
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. The LLC1 Cells Grown in Mice Lung Caused Albuminuria
2.2. The Collapse of Glomerular Tufts and Structural Lesions in Tubules Were Present in the Kidneys of the Lung Cancer Mice
2.3. Proteins Identified in Lung Cancer Cell Secretome Potentiated Nephrotoxicity
2.4. Fewer LLC1 Cells Implanted in Mice Develop Relatively Mitigaged Renal Insult and Inflammation
2.5. Mice Transplanted with Fewer LLC1 Cells Had Milder Renal Fibrosis
2.6. Activation of TGF-β Signaling in the Kidneys of the Lung Cancer Mice
2.7. Cancer Secretome-Activated Renal Inflammation
2.8. Exposure of Glomeruli to LLC1 Cell-Conditioned Medium Leads to Loss of Glomerular Integrity
3. Discussion
4. Material and Methods
4.1. Materials
4.2. Animal Care and Lung Cancer Cell Orthotropic Xenograft Model
4.3. Biopsy Collection, Histochemical Staining, and Immunohistochemical Staining
4.4. Evaluation of Serum Physiological Parameters
4.5. Cell Culture and Orthotopic Xenograft
4.6. Cell Culture and Proteomic Profiling of Secretome
4.7. Cell Culture and Secretome-Induced Inflammation
4.8. Renal Cells Primary Culture
4.9. Glomerular Integrity Assay
4.10. Immunofluorescent Staining and Immunofluorescent Microscopic Imagination
4.11. Immunoblot
4.12. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Gene Name | Protein Name | Signaling Pathway in Renal Pathogenesis | Kidney Disease Association | Ref. |
---|---|---|---|---|
ANGPL2 | Angiopoietin-related protein 2 | TGF-β pathway | Renal fibrosis | [37] |
BGN | Biglycan | TLR-2/4 signaling | Inflammation | [39,42,43] |
BMP1 | Bone morphogenetic protein1 | TGF-β pathway | Renal fibrosis | [38] |
C1r | Complement C1r | Complement system | Renal fibrosis | [44] |
C1s | Complement C1s | Complement system | Renal fibrosis | [44] |
DCN | Decorin | TGF-β pathway | Renal fibrosis | [39,43] |
DPP3 | Dipeptidyl peptidase 3 | Renin-angiotensin system | Inflammation | [45,46] |
FN1 | Fibronectin | TGF-β pathway | Glomerulopathy, mesangial expansion, renal fibrosis | [40,47] |
LGALS3 | Galectin-3 | Interstitial fibrosis, ciliopathy | [48] | |
MIF | Macrophage migration inhibitory factor | TLR-4-NF-β B signaling axis | Acute kidney injury, inflammation | [49] |
MCP1 | Monocyte chemoattractant protein 1 | TGF-β pathway | Inflammation, glomerular injury, renal fibrosis | [41,50] |
PDGFC | Platelet-derived growth factor C | PDGF signaling | Renal interstitial fibrosis | [51,52,53] |
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Hung, C.-C.; Zhen, Y.-Y.; Niu, S.-W.; Hsu, J.-F.; Lee, T.-H.; Chuang, H.-H.; Wang, P.-H.; Lee, S.-C.; Lin, P.-C.; Chiu, Y.-W.; et al. Lung Cancer Cell-Derived Secretome Mediates Paraneoplastic Inflammation and Fibrosis in Kidney in Mice. Cancers 2020, 12, 3561. https://doi.org/10.3390/cancers12123561
Hung C-C, Zhen Y-Y, Niu S-W, Hsu J-F, Lee T-H, Chuang H-H, Wang P-H, Lee S-C, Lin P-C, Chiu Y-W, et al. Lung Cancer Cell-Derived Secretome Mediates Paraneoplastic Inflammation and Fibrosis in Kidney in Mice. Cancers. 2020; 12(12):3561. https://doi.org/10.3390/cancers12123561
Chicago/Turabian StyleHung, Chi-Chih, Yen-Yi Zhen, Sheng-Wen Niu, Jui-Feng Hsu, Tai-Huang Lee, Hsiang-Hao Chuang, Pei-Hui Wang, Su-Chu Lee, Pi-Chen Lin, Yi-Wen Chiu, and et al. 2020. "Lung Cancer Cell-Derived Secretome Mediates Paraneoplastic Inflammation and Fibrosis in Kidney in Mice" Cancers 12, no. 12: 3561. https://doi.org/10.3390/cancers12123561
APA StyleHung, C.-C., Zhen, Y.-Y., Niu, S.-W., Hsu, J.-F., Lee, T.-H., Chuang, H.-H., Wang, P.-H., Lee, S.-C., Lin, P.-C., Chiu, Y.-W., Wu, C.-H., Huang, M.-S., Hsiao, M., Chen, H.-C., & Yang, C.-J. (2020). Lung Cancer Cell-Derived Secretome Mediates Paraneoplastic Inflammation and Fibrosis in Kidney in Mice. Cancers, 12(12), 3561. https://doi.org/10.3390/cancers12123561