Conditioned media from human ovarian cancer endothelial progenitor cells induces ovarian cancer cell migration by activating epithelial-to-mesenchymal transition.
Bone marrow-derived endothelial progenitor cells (EPCs) migrate to and engraft at ovarian cancer sites. Understanding the interactions between ovarian cancer cells and EPCs is fundamental for determining whether to harness EPC-tumor interactions for delivery of therapeutic agents or target them for intervention. Ovarian cancer cell lines (SKOV-3 and OVCAR-3) were cultured alone or in EPC-conditioned media (EPC-CM). Migration of ovarian cancer cells was detected by transwell chamber. N-cadherin and E-cadherin expression were analyzed by real-time reverse transcription PCR and western blot. EPC-CM can increase transforming growth factor-beta (TGF-β) secretion in SKOV-3 and OVCAR-3 cells. EPC-CM induced loss of ovarian cancer cell-cell junctions, downregulation of E-cadherin, upregulation of N-cadherin and acquisition of a fibroblastic phenotype, consistent with an epithelial-to-mesenchymal transition (EMT). The specific TGF-β inhibitor SB431542 abolished the SKOV-3 and OVCAR-3 ovarian cancer cell migration induced by EPC-CM. In SKOV-3 and OVCAR-3 cells, EPC-CM downregulated E-cadherin and concurrently upregulated N-cadherin. EPC-CM upregulated the expression of transcriptional repressors of E-cadherin, Snail and Twist. Treatment with SB431542 abolished the effects of EPC-CM on the relative expression levels of cadherin, Snail and Twist. This study demonstrates that TGF-β has a role in EPC-CM-induced ovarian cancer migration by activating EMT.
Department of Clinical Laboratory, Cancer Hospital, Harbin Medical University, Harbin, China.
L
L
Teng
Department of Clinical Laboratory, Cancer Hospital, Harbin Medical University, Harbin, China.
S
S
Peng
Department of Clinical Laboratory, Cancer Hospital, Harbin Medical University, Harbin, China.
H
H
Guo
Department of Clinical Laboratory, Cancer Hospital, Harbin Medical University, Harbin, China.
H
H
Liang
Department of Clinical Laboratory, Cancer Hospital, Harbin Medical University, Harbin, China.
Z
Z
Xu
Department of Clinical Laboratory, Cancer Hospital, Harbin Medical University, Harbin, China.
Y
Y
Su
Department of Clinical Laboratory, Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, China.
L
L
Gao
D001549:Benzamides / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D004149:Dioxoles / Q000494:pharmacology; D066026:Endothelial Progenitor Cells / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000378:metabolism
C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D017077:Culture Media, Conditioned; D004149:Dioxoles; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D051879:Twist-Related Protein 1