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Tumor angiogenesis of SCLC inhibited by decreased expression of FMOD via downregulating angiogenic factors of endothelial cells
- Source :
- Biomedicine & Pharmacotherapy. 87:539-547
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
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.
- Subjects :
- Male
Vascular Endothelial Growth Factor A
0301 basic medicine
Pathology
medicine.medical_specialty
Lung Neoplasms
Angiogenesis
Down-Regulation
Neovascularization, Physiologic
Mice, SCID
Biology
Cell Line
Transforming Growth Factor beta1
Extracellular matrix
Mice
03 medical and health sciences
Cell Movement
Cell Line, Tumor
Human Umbilical Vein Endothelial Cells
medicine
Animals
Humans
Gene silencing
Neoplasm Invasiveness
Autocrine signalling
Cell Proliferation
Pharmacology
Neovascularization, Pathologic
Endothelial Cells
Cancer
General Medicine
Middle Aged
medicine.disease
Small Cell Lung Carcinoma
030104 developmental biology
Proteoglycan
Cancer cell
biology.protein
Cancer research
Angiogenesis Inducing Agents
Female
Fibroblast Growth Factor 2
Wound healing
Fibromodulin
Subjects
Details
- ISSN :
- 07533322
- Volume :
- 87
- Database :
- OpenAIRE
- Journal :
- Biomedicine & Pharmacotherapy
- Accession number :
- edsair.doi.dedup.....4218bc9e828713f77e6a40c2fcfac053