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Int. J. Mol. Sci. 2014, 15(3), 4780-4794; doi:10.3390/ijms15034780
Article

Over-Expression of Platelet-Derived Growth Factor-D Promotes Tumor Growth and Invasion in Endometrial Cancer

1,†
, 2,†
, 3
, 4
 and 1,*
1 Department of Obstetrics and Gynecology, the Affiliated Hospital of Jiangnan University and the Fourth People's Hospital of Wuxi, Wuxi 214062, Jiangsu, China 2 Department of Obstetrics and Gynecology, International Peace Maternity & Child Health Hospital of the China Welfare Institute Affiliated to Shanghai Jiaotong University, Shanghai 200030, China 3 Department of Radiation Oncology, Zhongshan Hospital of Fudan University, Shanghai 200032, China 4 Department of Obstetrics and Gynecology, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, Henan, China These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 9 February 2014 / Revised: 20 February 2014 / Accepted: 10 March 2014 / Published: 18 March 2014
(This article belongs to the Section Molecular Pathology)
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Abstract

The platelet-derived growth factor-D (PDGF-D) was demonstrated to be able to promote tumor growth and invasion in human malignancies. However, little is known about its roles in endometrial cancer. In the present study, we investigated the expression and functions of PDGF-D in human endometrial cancer. Alterations of PDGF-D mRNA and protein were determined by real time PCR, western blot and immunohistochemical staining. Up-regulation of PDGF-D was achieved by stably transfecting the pcDNA3-PDGF-D plasmids into ECC-1 cells; and knockdown of PDGF-D was achieved by transient transfection with siRNA-PDGF-D into Ishikawa cells. The MTT assay, colony formation assay and Transwell assay were used to detect the effects of PDGF-D on cellular proliferation and invasion. The xenograft assay was used to investigate the functions of PDGF-D in vivo. Compared to normal endometrium, more than 50% cancer samples showed over-expression of PDGF-D (p < 0.001), and high level of PDGF-D was correlated with late stage (p = 0.003), deep myometrium invasion (p < 0.001) and lympha vascular space invasion (p = 0.006). In vitro, over-expressing PDGF-D in ECC-1 cells significantly accelerated tumor growth and promoted cellular invasion by increasing the level of MMP2 and MMP9; while silencing PDGF-D in Ishikawa cells impaired cell proliferation and inhibited the invasion, through suppressing the expression of MMP2 and MMP9. Moreover, we also demonstrated that over-expressed PDGF-D could induce EMT and knockdown of PDGF-D blocked the EMT transition. Consistently, in xenografts assay, PDGF-D over-expression significantly promoted tumor growth and tumor weights. We demonstrated that PDGF-D was commonly over-expressed in endometrial cancer, which was associated with late stage deep myometrium invasion and lympha vascular space invasion. Both in vitro and in vivo experiments showed PDGF-D could promote tumor growth and invasion through up-regulating MMP2/9 and inducing EMT. Thus, we propose targeting PDGF-D to be a potent strategy for endometrial cancer treatment.
Keywords: endometrial cancer; platelet-derived growth factor-D (PDGF-D); proliferation; invasion; matrix metalloproteinase (MMP); the epithelial-mesenchymal-transition (EMT) endometrial cancer; platelet-derived growth factor-D (PDGF-D); proliferation; invasion; matrix metalloproteinase (MMP); the epithelial-mesenchymal-transition (EMT)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Wang, Y.; Qiu, H.; Hu, W.; Li, S.; Yu, J. Over-Expression of Platelet-Derived Growth Factor-D Promotes Tumor Growth and Invasion in Endometrial Cancer. Int. J. Mol. Sci. 2014, 15, 4780-4794.

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