Platelet-derived growth factor-D overexpression contributes to epithelial-mesenchymal transition of PC3 prostate cancer cells.

Abstract

The majority of human malignancies are believed to have epithelial origin, and the progression of cancer is often associated with a transient process named epithelial-mesenchymal transition (EMT). EMT is characterized by the loss of epithelial markers and the gain of mesenchymal markers that are typical of "cancer stem-like cells," which results in increased cell invasion and metastasis in vivo. Therefore, it is important to uncover the mechanistic role of factors that may induce EMT in cancer progression. Studies have shown that platelet-derived growth factor (PDGF) signaling contributes to EMT, and more recently, PDGF-D has been shown to regulate cancer cell invasion and angiogenesis. However, the mechanism by which PDGF-D promotes invasion and metastases and whether it is due to the acquisition of EMT phenotype remain elusive. For this study, we established stably transfected PC3 cells expressing high levels of PDGF-D, which resulted in the significant induction of EMT as shown by changes in cellular morphology concomitant with the loss of E-cadherin and zonula occludens-1 and gain of vimentin. We also found activation of mammalian target of rapamycin and nuclear factor-kappaB, as well as Bcl-2 overexpression, in PDGF-D PC3 cells, which was associated with enhanced adhesive and invasive behaviors. More importantly, PDGF-D-overexpressing PC3 cells showed tumor growth in SCID mice much more rapidly than PC3 cells. These results provided a novel mechanism by which PDGF-D promotes EMT, which in turn increases tumor growth, and these results further suggest that PDGF-D could be a novel therapeutic target for the prevention and/or treatment of prostate cancer. Disclosure of potential conflicts of interest is found at the end of this article.

• Authors: Dejuan Kong, Zhiwei Wang, Sarah H Sarkar, Yiwei Li, Sanjeev Banerjee, Allen Saliganan, Hyeong-Reh Choi Kim, Michael L Cher, Fazlul H Sarkar
• Journal: Stem cells (Dayton, Ohio) (Stem Cells) Vol. 26 Issue 6 Pg. 1425-35 (Jun 2008) ISSN: 1549-4918 [Electronic] England
• PMID: 18403754 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Lymphokines
• PDGFD protein, human
• Platelet-Derived Growth Factor
• RNA, Neoplasm
• RNA, Small Interfering

Topics

• Epithelial Cells (cytology, pathology)
• Gene Expression Regulation, Neoplastic
• Humans
• Lymphokines (genetics, physiology)
• Male
• Mesoderm (cytology, pathology)
• Neoplasm Invasiveness
• Plasmids
• Platelet-Derived Growth Factor (genetics, physiology)
• Polymerase Chain Reaction
• Prostatic Neoplasms (genetics, pathology)
• RNA, Neoplasm (genetics)
• RNA, Small Interfering (genetics)
• Transfection