| Title: | Novel antiangiogenic therapy targeting biglycan using tumor endothelial cell-specific liposomal siRNA delivery system |
| Authors: | Maishi, Nako Browse this author →KAKEN DB |
| Sakurai, Yu Browse this author →KAKEN DB |
| Hatakeyama, Hiroto Browse this author →KAKEN DB |
| Umeyama, Yui Browse this author →KAKEN DB |
| Nakamura, Takashi Browse this author →KAKEN DB |
| Endo, Rikito Browse this author |
| Alam, Mohammad Towfik Browse this author →KAKEN DB |
| Li, Cong Browse this author |
| Annan, Dorcas Akuba-Muhyia Browse this author →KAKEN DB |
| Kikuchi, Hiroshi Browse this author →KAKEN DB |
| Morimoto, Hirofumi Browse this author |
| Morimoto, Masahiro Browse this author |
| Akiyama, Kosuke Browse this author →KAKEN DB |
| Ohga, Noritaka Browse this author →KAKEN DB |
| Hida, Yasuhiro Browse this author →KAKEN DB |
| Harashima, Hideyoshi Browse this author →KAKEN DB |
| Hida, Kyoko Browse this author →KAKEN DB |
| Keywords: | biglycan |
| drug delivery system |
| tumor angiogenesis |
| tumor endothelial cell |
| tumor microenvironment |
| Issue Date: | 9-Mar-2022 |
| Publisher: | John Wiley & Sons |
| Journal Title: | Cancer science |
| Publisher DOI: | 10.1111/cas.15323 |
| PMID: | 35266253 |
| 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 alpha(V)beta(3) 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. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/85082 |
| Appears in Collections: | 歯学院・歯学研究院 (Graduate School of Dental Medicine / Faculty of Dental Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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