JaLCDOI 10.18926/AMO/56071
FullText URL 72_3_257.pdf
Author Asano, Keiichi| Edamatsu, Midori| F. Hatipoglu, Omer| Inagaki, Junko| Ono, Mitsuaki| Ohtsuki, Takashi| Oohashi, Toshitaka| Hirohata, Satoshi|
Abstract Several research groups demonstrated that ‘a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs (ADAMTS)’-family proteases play roles in cancer progression. However, the origins and contributions of these proteases are not known. Here, we demonstrate an association between host-produced ADAMTS4 and early-stage tumor growth. Murine Lewis lung carcinoma (LLC) tumors showed marked expressions of Adamts4 and Adamts5. We examined the contributions and distributions of host-derived Adamts4 and Adamts5 on tumor growth, using Adamts4LacZ/LacZ and Adamts5LacZ/LacZ knockout mice. Interestingly, the Adamts4LacZ/LacZ mice showed enhanced tumor growth compared to wild-type mice at 5-, 10- and 12-days post-inoculation, whereas the Adamts5LacZ/LacZ mice did not show significant differences in tumor growth. We next examined LacZ distribution in LLC tumor-bearing Adamts4LacZ/LacZ mice by β-galactosidase (β-gal) staining. We found that the β-gal-positive signals were strictly localized at the interior areas of the tumor at 10 days post-inoculation. Multiple staining demonstrated that most of the β-gal-positive cells were localized at the tumor vasculature in Adamts4LacZ/LacZ mice. Interestingly, β-gal-positive signals were not co-localized with biglycan after 10 days post-inoculation, excluding the biglycan cleavage by host-derived ADAMTS4. Taken together, these findings illustrate that host-derived ADAMTS4 was expressed at the tumor vessels and was associated with early-stage tumor growth.
Keywords ADAMTS metalloproteinase extracellular matrix tumor microenvironment mouse
Amo Type Original Article
Published Date 2018-06
Publication Title Acta Medica Okayama
Volume volume72
Issue issue3
Publisher Okayama University Medical School
Start Page 257
End Page 266
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
Copyright Holders CopyrightⒸ 2018 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 29926003