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.

Original languageEnglish
Pages (from-to)257-266
Number of pages10
JournalActa Medica Okayama
Volume72
Issue number3
Publication statusPublished - Jan 1 2018

Fingerprint

Tumors
Growth
Neoplasms
Biglycan
Lewis Lung Carcinoma
Peptide Hydrolases
Bearings (structural)
Galactosidases
Thrombospondin 1
Disintegrins
Staining and Labeling
Metalloproteases
Knockout Mice
Cells
Research

Keywords

  • ADAMTS
  • Extracellular matrix
  • Metalloproteinase
  • Mouse
  • Tumor microenvironment

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Host-produced ADAMTS4 inhibits early-stage tumor growth. / Asano, Keiichi; Edamatsu, Midori; Hatipoglu, Omer F.; Inagaki, Junko; Ono, Mitsuaki; Ohtsuki, Takashi; Oohashi, Toshitaka; Hirohata, Satoshi.

In: Acta Medica Okayama, Vol. 72, No. 3, 01.01.2018, p. 257-266.

Research output: Contribution to journalArticle

@article{4da1fb2048974c9daf5ce48d4b646d5b,
title = "Host-produced ADAMTS4 inhibits early-stage tumor growth",
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, Extracellular matrix, Metalloproteinase, Mouse, Tumor microenvironment",
author = "Keiichi Asano and Midori Edamatsu and Hatipoglu, {Omer F.} and Junko Inagaki and Mitsuaki Ono and Takashi Ohtsuki and Toshitaka Oohashi and Satoshi Hirohata",
year = "2018",
month = "1",
day = "1",
language = "English",
volume = "72",
pages = "257--266",
journal = "Acta Medica Okayama",
issn = "0386-300X",
publisher = "Okayama University",
number = "3",

}

TY - JOUR

T1 - Host-produced ADAMTS4 inhibits early-stage tumor growth

AU - Asano, Keiichi

AU - Edamatsu, Midori

AU - Hatipoglu, Omer F.

AU - Inagaki, Junko

AU - Ono, Mitsuaki

AU - Ohtsuki, Takashi

AU - Oohashi, Toshitaka

AU - Hirohata, Satoshi

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - ADAMTS

KW - Extracellular matrix

KW - Metalloproteinase

KW - Mouse

KW - Tumor microenvironment

UR - http://www.scopus.com/inward/record.url?scp=85048855885&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85048855885&partnerID=8YFLogxK

M3 - Article

VL - 72

SP - 257

EP - 266

JO - Acta Medica Okayama

JF - Acta Medica Okayama

SN - 0386-300X

IS - 3

ER -