| RRC ID |
71619
|
| 著者 |
Maishi N, Sakurai Y, Hatakeyama H, Umeyama Y, Nakamura T, Endo R, Alam MT, Li C, Annan DA, Kikuchi H, Morimoto H, Morimoto M, Akiyama K, Ohga N, Hida Y, Harashima H, Hida K.
|
| タイトル |
Novel antiangiogenic therapy targeting biglycan using tumor endothelial cell-specific liposomal siRNA delivery system.
|
| ジャーナル |
Cancer Sci
|
| Abstract |
Tumor blood vessels play important roles in tumor progression and metastasis. Targeting tumor endothelial cells (TECs) is one of the strategies for cancer therapy. We previously reported that biglycan, a small leucine-rich proteoglycan, is highly expressed in TECs. TECs utilize biglycan in an autocrine manner for migration and angiogenesis. Furthermore, TEC-derived biglycan stimulates tumor cell migration in a paracrine manner leading to tumor cell intravasation and metastasis. In this study, we explored the therapeutic effect of biglycan inhibition in the TECs of renal cell carcinoma using an in vivo siRNA delivery system known as a multifunctional envelope-type nanodevice (MEND), which contains a unique pH-sensitive cationic lipid. To specifically deliver MEND into TECs, we incorporated cyclo(Arg-Gly-Asp-D-Phe-Lys) (cRGD) into MEND because αV β3 integrin, a receptor for cRGD, is selective and highly expressed in TECs. We developed RGD-MEND-encapsulating siRNA against biglycan. First, we confirmed that MEND was delivered into OS-RC-2 tumor-derived TECs and induced in vitro RNAi-mediated gene silencing. MEND was then injected intravenously into OS-RC-2 tumor-bearing mice. Flow cytometry analysis demonstrated that MEND was specifically delivered into TECs. Quantitative RT-PCR indicated that biglycan was knocked down by biglycan siRNA-containing MEND. Finally, we analyzed the therapeutic effect of biglycan silencing by MEND in TECs. Tumor growth was inhibited by biglycan siRNA-containing MEND. Tumor microenvironmental factors such as fibrosis were also normalized using biglycan inhibition in TECs. Biglycan in TECs can be a novel target for cancer treatment.
|
| 巻・号 |
113(5)
|
| ページ |
1855-1867
|
| 公開日 |
2022-5-1
|
| DOI |
10.1111/cas.15323
|
| PMID |
35266253
|
| PMC |
PMC9128192
|
| MeSH |
Angiogenesis Inhibitors
Animals
Biglycan / genetics
Carcinoma, Renal Cell* / genetics
Carcinoma, Renal Cell* / therapy
Endothelial Cells
Humans
Kidney Neoplasms* / genetics
Liposomes
Mice
RNA, Small Interfering / genetics
|
| IF |
4.966
|
| リソース情報 |
| ヒト・動物細胞 |
OS-RC-2(RCB0735) |
