title: Tumor angiogenesis of SCLC inhibited by decreased expression of FMOD via downregulating angiogenic factors of endothelial cells.
abstract: Fibromodulin (FMOD), an ECM small leucine-rich proteoglycan (SLRP), was reported to promote angiogenesis not only during wound healing, but also in optical and cutaneous angiogenesis-dependent diseases. However, whether it plays important roles in tumor angiogenesis remains unclear. To explore the role of FMOD in tumor angiogenesis of human small cell lung cancer (SCLC), initially the study analyzed the relationship of FMOD expression in cancer tissues of SCLC with clinical characteristics. The analysis revealed that the positive FMOD expression was significantly associated with extensive stage of SCLC and higher vascular density. In mouse models, xenograft tumors developed with FMOD-silenced H446 cells (H446-shFMOD) exhibited slowed growth rate, decreased microvessel density, and reduced blood perfusion related to that of controls (H446-shCON). Additionally, compared with that of controls, the decreased secretion of FMOD in conditioned medium (CM) from H446-shFMOD inhibited proliferation, migration, and invasion of human umbilical vessel endothelial cells (HUVECs). Moreover, the decreased secretion of FMOD downregulated the expression of VEGF, TGF-β1, FGF-2, and PDGF-B in HUVECs. The findings strongly suggested that the autocrine FMOD of cancer cells may promote tumor angiogenesis of SCLC by upregulating the expression of angiogenic factors that act in concert to facilitate the angiogenic phenotype of endothelial cells as a proangiogenic factor. Therefore, silencing FMOD may be a potentially clinical therapy for repressing tumor angiogenesis.
authors.affiliation: Institute of Respiratory Disease, Xinqiao Hospital, The Third Military Medical University, Chongqing, 400037, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Ao
authors.affiliation: Institute of Respiratory Disease, Xinqiao Hospital, The Third Military Medical University, Chongqing, 400037, China.
authors.forename: Shilong
authors.initials: S
authors.lastname: Yu
authors.affiliation: Institute of Field Internal Medicine, Xinqiao Hospital, The Third Military Medical University, Chongqing, 400037, China.
authors.forename: Pin
authors.initials: P
authors.lastname: Qian
authors.affiliation: Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, Chongqing, 400037, China.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Respiratory Diseases, 324th Hospital of the People's Liberation Army, Chongqing, 400020, China.
authors.forename: Ruiling
authors.initials: R
authors.lastname: Guo
authors.affiliation: Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, Chongqing, 400037, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Pathology, Xinqiao Hospital, The Third Military Medical University, Chongqing, 400037, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Xu
authors.affiliation: Institute of Respiratory Disease, Xinqiao Hospital, The Third Military Medical University, Chongqing, 400037, China.
authors.forename: Ruijie
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Institute of Respiratory Disease, Xinqiao Hospital, The Third Military Medical University, Chongqing, 400037, China.
authors.forename: Chaowen
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Institute of Respiratory Disease, Xinqiao Hospital, The Third Military Medical University, Chongqing, 400037, China. Electronic address: jifuyun@263.net.
authors.forename: Fuyun
authors.initials: F
authors.lastname: Ji
authors.affiliation: Institute of Respiratory Disease, Xinqiao Hospital, The Third Military Medical University, Chongqing, 400037, China. Electronic address: qiangs1220@163.com.
authors.forename: Guisheng
authors.initials: G
authors.lastname: Qian
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology*; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D000071235:Fibromodulin / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000502:physiology; D055752:Small Cell Lung Carcinoma / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D000071235:Fibromodulin
keywords: Extracellular matrix; Fibromodulin; Proangiogenic factor; Small cell lung cancer; Tumor angiogenesis