| First Author | Asano K | Year | 2018 |
| Journal | Acta Med Okayama | Volume | 72 |
| Issue | 3 | Pages | 257-266 |
| PubMed ID | 29926003 | Mgi Jnum | J:345754 |
| Mgi Id | MGI:6831885 | Doi | 10.18926/AMO/56071 |
| Citation | Asano K, et al. (2018) Host-produced ADAMTS4 Inhibits Early-Stage Tumor Growth. Acta Med Okayama 72(3):257-266 |
| abstractText | 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 beta-galactosidase (beta-gal) staining. We found that the beta-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 beta-gal-positive cells were localized at the tumor vasculature in Adamts4LacZ/LacZ mice. Interestingly, beta-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. |
