RRC ID 55902
Author Kandori S, Kojima T, Matsuoka T, Yoshino T, Sugiyama A, Nakamura E, Shimazui T, Funakoshi Y, Kanaho Y, Nishiyama H.
Title Phospholipase D2 promotes disease progression of renal cell carcinoma through the induction of angiogenin.
Journal Cancer Sci
Abstract A hallmark of clear cell renal cell carcinoma (ccRCC) is the presence of intracellular lipid droplets (LD) and it is assumed that phosphatidic acid (PA) produced by phospholipase D (PLD) plays some role in the LD formation. However, little is known about the significance of PLD in ccRCC. In this study, we examined the expression levels of PLD in ccRCC. The classical mammalian isoforms of PLD are PLD1 and PLD2, and the levels of both mRNA were higher at the primary tumor sites than in normal kidney tissues. Similarly, both PLD were significantly abundant in tumor cells as determined by analysis using immunohistochemical staining. Importantly, a higher level of PLD was significantly associated with a higher tumor stage and grade. Because PLD2 knockdown effectively suppressed the cell proliferation and invasion of ccRCC as compared with PLD1 in vitro, we examined the effect of PLD2 in vivo. Notably, shRNA-mediated knockdown of PLD2 suppressed the growth and invasion of tumors in nude mouse xenograft models. Moreover, the higher expression of PLD2 was significantly associated with poorer prognosis in 67 patients. As for genes relating to the tumor invasion of PLD2, we found that angiogenin (ANG) was positively regulated by PLD2. In fact, the expression levels of ANG were elevated in tumor tissues as compared with normal kidney and the inhibition of ANG activity with a neutralizing antibody significantly suppressed tumor invasion. Overall, we revealed for the first time that PLD2-produced PA promoted cell invasion through the expression of ANG in ccRCC cells.
Volume 109(6)
Pages 1865-1875
Published 2018-6
DOI 10.1111/cas.13609
PMID 29660846
PMC PMC5989877
MeSH Aged Animals Carcinoma, Renal Cell / genetics* Carcinoma, Renal Cell / metabolism Carcinoma, Renal Cell / pathology Cell Line, Tumor Disease Progression Gene Expression Regulation, Neoplastic* HEK293 Cells Humans Kaplan-Meier Estimate Kidney Neoplasms / genetics* Kidney Neoplasms / metabolism Kidney Neoplasms / pathology Mice, Nude Middle Aged Phospholipase D / genetics* Phospholipase D / metabolism RNA Interference RNAi Therapeutics / methods Ribonuclease, Pancreatic / genetics* Ribonuclease, Pancreatic / metabolism Xenograft Model Antitumor Assays
IF 4.751
Times Cited 8
Human and Animal Cells 293T(RCB2202)