title: Downregulation of caveolin‑1 upregulates the expression of growth factors and regulators in co‑culture of fibroblasts with cancer cells.
abstract: Reduced expression levels of caveolin‑1 (Cav‑1) in tumor stromal fibroblasts influences the occurrence and progression of tumors, particularly in breast cancer, but the relevant molecular mechanism is unclear. The present study aimed to clarify the potential mechanism underlying the promotion of tumor growth by reduced Cav‑1 expression levels, by investigating Cav‑1‑targeted molecules in fibroblasts and breast cancer cells. The expression of growth factors in the ESF fibroblast cell line transfected with Cav‑1 small interfering RNA (siRNA) was examined. The expression of apoptotic regulators in the BT474 breast cancer cell line that was co‑cultured with the fibroblasts, was also investigated. The transfection of Cav‑1‑targeting siRNA in ESF cells resulted in efficient and specific inhibition of Cav‑1 expression. The downregulation of Cav‑1 increased the expression and secretion of stromal cell‑derived factor‑1 (SDF‑1), epidermal growth factor (EGF) and fibroblast‑specific protein‑1 (FSP‑1) in ESF cells. This resulted in the accelerated proliferation of the breast cancer cells. Tumor protein 53‑induced glycolysis and apoptosis regulator (TIGAR) was upregulated in the BT474 cells under the condition of co‑culture with Cav‑1 siRNA fibroblasts, while levels of reactive oxygen species (ROS) were decreased, resulting in apoptosis inhibition in the breast cancer cells. These results demonstrated that the downregulation of Cav‑1 promoted the growth of breast cancer cells through increasing SDF‑1, EGF and FSP‑1 in tumor stromal fibroblasts, and TIGAR levels in breast cancer cells. To the best of our knowledge, the present study supports the hypothesis that Cav‑1 possesses tumor‑suppressor properties, with the mechanism of Cav‑1‑dependent signaling involving the regulation of SDF‑1, EGF, FSP‑1 and TIGAR.
authors.affiliation: Key Laboratory of Medical Biology, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Shi
authors.affiliation: Department of Pathophysiology, Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Xiong
authors.affiliation: Molecular Center Laboratory, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Medical Biology, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Chuang
authors.initials: C
authors.lastname: Meng
authors.affiliation: Key Laboratory of Medical Biology, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Guan-Yun
authors.initials: GY
authors.lastname: Qi
authors.affiliation: Key Laboratory of Medical Biology, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Wen-Lin
authors.initials: WL
authors.lastname: Li
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D018920:Coculture Techniques; D015536:Down-Regulation; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D000071999:S100 Calcium-Binding Protein A4; D015854:Up-Regulation
chemical_list: D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins; D051242:Caveolin 1; D054377:Chemokine CXCL12; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000071999:S100 Calcium-Binding Protein A4; C077591:S100A4 protein, human; D004815:Epidermal Growth Factor; D010744:Phosphoric Monoester Hydrolases; C512708:TIGAR protein, human