{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:58:53Z","timestamp":1787165933040,"version":"build-2736575974"},"reference-count":70,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,11,28]],"date-time":"2020-11-28T00:00:00Z","timestamp":1606521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Kidney failure is a possible but rare complication in lung cancer patients that may be caused by massive tumor lysis or a paraneoplastic effect. Clinical case reports have documented pathological characteristics of paraneoplastic syndrome in glomeruli, but are short of molecular details. When Lewis lung carcinoma 1 (LLC1) cells were implanted in mice lungs to establish lung cancer, renal failure was frequently observed two weeks post orthotopic xenograft. The high urinary albumin-to-creatinine ratio (ACR) was diagnosed as paraneoplastic nephrotic syndrome in those lung cancer mice. Profiling the secretome of the lung cancer cells revealed that the secretory proteins were potentially nephrotoxic. The nephrotoxicity of lung cancer-derived secretory proteins was tested by examining the pathogenic effects of 1 \u00d7 106, 2 \u00d7 106, and 5 \u00d7 106 LLC1 cell xenografts on the pathogenic progression in kidneys. Severe albuminuria was present in the mice that received 5 \u00d7 106 LLC1 cells implantation, whereas 106 cell and 2 \u00d7 106 cell-implanted mice have slightly increased albuminuria. Pathological examinations revealed that the glomeruli had capillary loop collapse, tumor antigen deposition in glomeruli, and renal intratubular casts. Since IL-6 and MCP-1 are pathologic markers of glomerulopathy, their distributions were examined in the kidneys of the lung cancer mice. Moderate to severe inflammation in the kidneys was correlated with increases in the number of cells implanted in the mice, which was reflected by renal IL-6 and MCP-1 levels, and urine ACR. TGF-\u03b2 signaling-engaged renal fibrosis was validated in the lung cancer mice. These results indicated that lung cancer cells could provoke inflammation and activate renal fibrosis.<\/jats:p>","DOI":"10.3390\/cancers12123561","type":"journal-article","created":{"date-parts":[[2020,11,29]],"date-time":"2020-11-29T21:55:31Z","timestamp":1606686931000},"page":"3561","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Lung Cancer Cell-Derived Secretome Mediates Paraneoplastic Inflammation and Fibrosis in Kidney in Mice"],"prefix":"10.3390","volume":"12","author":[{"given":"Chi-Chih","family":"Hung","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Yi","family":"Zhen","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Wen","family":"Niu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung 80145, Taiwan"},{"name":"Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jui-Feng","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung 80145, Taiwan"},{"name":"Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tai-Huang","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiang-Hao","family":"Chuang","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8587-7324","authenticated-orcid":false,"given":"Su-Chu","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pi-Chen","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6840-5440","authenticated-orcid":false,"given":"Yi-Wen","family":"Chiu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Hsing","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung 83301, Taiwan, and College of Medicine, Chang-Gung University, Taoyuan 33303, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Shyan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, E-Da Cancer Hospital, School of Medicine, I-Shou University, Kaohsiung 82445, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8529-9213","authenticated-orcid":false,"given":"Michael","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan"},{"name":"Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Chun","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Jen","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10528","DOI":"10.1073\/pnas.0504367102","article-title":"Proliferation and invasion: Plasticity in tumor cells","volume":"102","author":"Gao","year":"2005","journal-title":"Proc. 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