| RRC ID |
55902
|
| 著者 |
Kandori S, Kojima T, Matsuoka T, Yoshino T, Sugiyama A, Nakamura E, Shimazui T, Funakoshi Y, Kanaho Y, Nishiyama H.
|
| タイトル |
Phospholipase D2 promotes disease progression of renal cell carcinoma through the induction of angiogenin.
|
| ジャーナル |
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.
|
| 巻・号 |
109(6)
|
| ページ |
1865-1875
|
| 公開日 |
2018-6-1
|
| 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
|
| 引用数 |
8
|
| リソース情報 |
| ヒト・動物細胞 |
293T(RCB2202) |
