title: Mesenchymal stem cells promote tumor angiogenesis via the action of transforming growth factor β1.
abstract: Mesenchymal stem cells (MSCs) may influence the growth and metastasis of various human malignancies, including hepatocellular carcinoma (HCC). Therefore, the underlying mechanisms via which MSCs are able to affect malignancies require investigation. In the present study, the potential role of MSC in the angiogenesis of HCC was investigated. A total of 17 nude mouse models exhibiting human HCC were used to evaluate the effects of MSC on angiogenesis. A total of 8 mice were injected with human MSCs via the tail vein, and the remaining 9 mice were injected with phosphate-buffered saline as a control. A total of 35 days subsequent to the injection of MSCs, the microvessel density (MVD) of tumors was evaluated by immunostaining, using cluster of differentiation 31 antibody. The mRNA levels of transforming growth factor (TGF)β1, Smad2 and Smad7 were detected using reverse transcription-quantitative polymerase chain reaction. Protein expression levels of TGFβ1 and vascular endothelial growth factor (VEGF) in tumor tissues were analyzed using ELISA. Compared with controls, MVD in MSC-treated mice was significantly increased (28.00±9.19 vs. 18.11±3.30; P=0.006). The levels of TGFβ1 mRNA in the MSC-treated group were 2.15-fold higher compared with the control group (1.27±0.61 vs. 0.59±0.39; P=0.033), and MVD was higher in the group exhibiting increased TGFβ1 mRNA levels compared with the control group (26.50±9.11 vs. 19.44±6.14; P=0.038). In addition, a close correlation between the expression levels of TGFβ1 and VEGF was identified. The results of the present study suggested that MSCs may be capable of enhancing the angiogenesis of HCC, which may be partly due to the involvement of TGFβ1.
authors.affiliation: Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Guo-Cai
authors.initials: GC
authors.lastname: Li
authors.affiliation: Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Zhang
authors.affiliation: Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Qing-Chun
authors.initials: QC
authors.lastname: Zhao
authors.affiliation: Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: L I
authors.initials: LI
authors.lastname: Sun
authors.affiliation: Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Liu
authors.initials: L
authors.lastname: Hong
authors.affiliation: Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Feng
authors.affiliation: Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cai
keywords: angiogenesis; hepatocellular carcinoma; mesenchymal stem cell; microvessel density; transforming growth factor; vascular endothelial growth factor