Forced expression of KIAA1199, a novel hyaluronidase, inhibits tumorigenicity of low-grade chondrosarcoma.


Journal

Journal of orthopaedic research : official publication of the Orthopaedic Research Society
ISSN: 1554-527X
Titre abrégé: J Orthop Res
Pays: United States
ID NLM: 8404726

Informations de publication

Date de publication:
09 2020
Historique:
received: 10 10 2019
revised: 30 01 2020
accepted: 11 02 2020
pubmed: 19 2 2020
medline: 15 12 2020
entrez: 19 2 2020
Statut: ppublish

Résumé

Hyaluronan (HA) has been shown to play crucial roles in the tumorigenicity of malignant tumors. Chondrosarcoma, particularly when low-grade, is characterized by the formation of an extracellular matrix (ECM) containing abundant HA, and its drug/radiation resistance has become a clinically relevant problem. This study aimed to evaluate the effects of a novel hyaluronidase, KIAA1199, on ECM formation as well as antitumor effects on chondrosarcoma. To clarify the roles of KIAA1199 in chondrosarcoma, mouse KIAA1199 was stably transfected to Swarm rat chondrosarcoma (RCS) cells (histologically grade 1). We investigated the effects of KIAA1199 on RCS cells in vitro and an autografted model in vivo. HA binding protein (HABP) stainability and ECM formation in KIAA1199-RCS was markedly suppressed compared with that of control cells. No significant changes in messenger RNA expression of Has1, Has2, Has3, Hyal1, or Hyal2 were observed. KIAA1199 expression did not affect proliferation or apoptosis but inhibited migration and invasion of RCS cells. In contrast, the expression of KIAA1199 significantly inhibited the growth of grafted tumors and suppressed the stainability of alcian blue in tumor tissues. Although there was no direct inhibitory effect on proliferation in vitro, induction of KIAA1199 showed the antitumor effects in grafted tumor growth in vivo possibly due to changes in the tumor microenvironment such as inhibition of ECM formation. Forced expression of KIAA1199 exhibits antitumor effects on low-grade chondrosarcoma, which has chemo- and radio-therapy resistant features. Together, KIAA1199 could be a novel promising therapeutic tool for low-grade chondrosarcoma, mediated by the degradation of HA.

Identifiants

pubmed: 32068299
doi: 10.1002/jor.24629
doi:

Substances chimiques

Hyaluronic Acid 9004-61-9
Cemip protein, mouse EC 3.2.1.35
Hyaluronoglucosaminidase EC 3.2.1.35

Types de publication

Evaluation Study Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1942-1951

Informations de copyright

© 2020 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

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Auteurs

Hiroshi Koike (H)

Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.

Yoshihiro Nishida (Y)

Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Department of Rehabilitation Medicine, Nagoya University Hospital, Nagoya, Aichi, Japan.

Tamayuki Shinomura (T)

Department of Hard Tissue Engineering, Tokyo Medical and Dental University, Tokyo, Japan.

Lisheng Zhuo (L)

Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.

Shunsuke Hamada (S)

Department of Orthopedic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

Kunihiro Ikuta (K)

Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.

Kan Ito (K)

Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.

Koji Kimata (K)

Multidisciplinary Pain Center, Aichi Medical University, Nagakute, Aichi, Japan.

Takahiro Ushida (T)

Multidisciplinary Pain Center, Aichi Medical University, Nagakute, Aichi, Japan.

Naoki Ishiguro (N)

Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.

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