Acta Medica Okayama 72巻 3号
2018-06 発行

Host-produced ADAMTS4 Inhibits Early-Stage Tumor Growth

Asano, Keiichi Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Edamatsu, Midori Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
F. Hatipoglu, Omer Department of Medical Technology, Graduate School of Health Sciences, Okayama University
Inagaki, Junko Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ono, Mitsuaki Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ohtsuki, Takashi Department of Medical Technology, Graduate School of Health Sciences, Okayama University
Oohashi, Toshitaka Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Hirohata, Satoshi Department of Medical Technology, Graduate School of Health Sciences, Okayama University
Publication Date
2018-06
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.
Document Type
Original Article
Keywords
ADAMTS
metalloproteinase
extracellular matrix
tumor microenvironment
mouse
Link to PubMed
Thumnail 72_3_257.pdf 3.61 MB