ID | 61398 |
FullText URL | |
Author |
Ono, Kisho
Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kaken ID
researchmap
Sogawa, Chiharu
Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kawai, Hotaka
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
Manh Tien Tran
Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Taha, Eman A.
Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Lu, Yanyin
Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
May Wathone Oo
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
Okusha, Yuka
Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kaken ID
researchmap
Okamura, Hirohiko
Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
ORCID
Kaken ID
publons
researchmap
Ibaragi, Soichiro
Department of Oral and Maxillofacial Surgery, Okayama University Hospital
ORCID
Kaken ID
publons
researchmap
Takigawa, Masaharu
Advanced Research Center for Oral and Craniofacial Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kaken ID
publons
researchmap
Kozaki, Ken-Ichi
Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Nagatsuka, Hitoshi
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
Kaken ID
publons
researchmap
Sasaki, Akira
Department of Oral and Maxillofacial Surgery, Okayama University Hospital
Kaken ID
publons
researchmap
Okamoto, Kuniaki
Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kaken ID
researchmap
Calderwood, Stuart K.
Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School
Eguchi, Takanori
Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
ORCID
Kaken ID
publons
researchmap
|
Abstract | Evidence has been accumulating to indicate that extracellular vesicles (EVs), including exosomes, released by cancer cells can foster tumour progression. The molecular chaperones – CDC37, HSP90α and HSP90β play key roles in cancer progression including epithelial‐mesenchymal transition (EMT), although their contribution to EVs‐mediated cell–cell communication in tumour microenvironment has not been thoroughly examined. Here we show that triple depletion of the chaperone trio attenuates numerous cancer malignancy events exerted through EV release. Metastatic oral cancer‐derived EVs (MEV) were enriched with HSP90α HSP90β and cancer‐initiating cell marker CD326/EpCAM. Depletion of these chaperones individually induced compensatory increases in the other chaperones, whereas triple siRNA targeting of these molecules markedly diminished the levels of the chaperone trio and attenuated EMT. MEV were potent agents in initiating EMT in normal epithelial cells, a process that was attenuated by the triple chaperone depletion. The migration, invasion, and in vitro tumour initiation of oral cancer cells were significantly promoted by MEV, while triple depletion of CDC37/HSP90α/β reversed these MEV‐driven malignancy events. In metastatic oral cancer patient‐derived tumours, HSP90β was significantly accumulated in infiltrating tumour‐associated macrophages (TAM) as compared to lower grade oral cancer cases. HSP90‐enriched MEV‐induced TAM polarization to an M2 phenotype, a transition known to support cancer progression, whereas the triple chaperone depletion attenuated this effect. Mechanistically, the triple chaperone depletion in metastatic oral cancer cells effectively reduced MEV transmission into macrophages. Hence, siRNA‐mediated knockdown of the chaperone trio (CDC37/HSP90α/HSP90β) could potentially be a novel therapeutic strategy to attenuate several EV‐driven malignancy events in the tumour microenvironment.
|
Keywords | Extracellular vesicles
epithelial‐mesenchymal transition
tumour‐associated macrophage
CDC37
HSP90
tetraspanin
oral cancer
|
Published Date | 2020-05-31
|
Publication Title |
Journal of Extracellular Vesicles
|
Volume | volume9
|
Issue | issue1
|
Publisher | Taylor & Francis
|
Start Page | 1769373
|
ISSN | 2001-3078
|
Content Type |
Journal Article
|
language |
English
|
OAI-PMH Set |
岡山大学
|
Copyright Holders | © 2020 The Author(s).
|
File Version | publisher
|
PubMed ID | |
DOI | |
Related Url | isVersionOf https://doi.org/10.1080/20013078.2020.1769373
|
License | http://creativecommons.org/licenses/by‐nc/4.0/
|
Funder Name |
Japan Society for the Promotion of Science
|
助成番号 | 17K11642
17K11643
17K11669
19K24072
16K11722-JM
19K10288-JM
18K09789-KN
JP16K11441
JP20H03888
19H03817
19H04051
20K09904
|