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Novel mechanism of cisplatin resistance in head and neck squamous cell carcinoma involving extracellular vesicles and a copper transporter system.
Ogawa, Tatsuo; Ono, Kisho; Ryumon, Shoji; Kawai, Hotaka; Nakamura, Tomoya; Umemori, Koki; Yoshida, Kunihiro; Kanemoto, Hideka; Obata, Kyoichi; Yoshioka, Norie; Okui, Tatsuo; Okamoto, Kuniaki; Nagatsuka, Hitoshi; Ibaragi, Soichiro.
Affiliation
  • Ogawa T; Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
  • Ono K; Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
  • Ryumon S; Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
  • Kawai H; Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
  • Nakamura T; Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
  • Umemori K; Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
  • Yoshida K; Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
  • Kanemoto H; Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
  • Obata K; Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
  • Yoshioka N; Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
  • Okui T; Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
  • Okamoto K; Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine, Izumo, Shimane, Japan.
  • Nagatsuka H; Department of Dental Pharmacology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
  • Ibaragi S; Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Head Neck ; 46(3): 636-650, 2024 Mar.
Article in En | MEDLINE | ID: mdl-38164660
ABSTRACT

BACKGROUND:

Cisplatin (CDDP) plays a central role in chemotherapy for head and neck squamous cell carcinoma (HNSCC), but drug resistance in HNSCC chemotherapy remains a problem, and the mechanism of CDDP resistance is unclear. We investigated CDDP-resistance mechanisms mediated by extracellular vesicles (EVs) and ATPase copper transporting beta (ATP7B) in HNSCC.

METHODS:

We established CDDP-resistant sublines of HNSCC cells and verified their ATP7B expression. We used an EV secretion inhibitor (GW4869) and ATP7B short hairpin (sh)RNA transfection to examine the correlation between EV secretion and ATP7B expression.

RESULTS:

The CDDP-resistant HNSCC sublines showed decreased CDDP sensitivity and increased ATP7B expression. GW4869 suppressed ATP7B expression, and ATP7B shRNA transfection suppressed EV secretion. The suppressions of EV secretion and ATP7B expression both enhanced CDDP's cell-killing effect.

CONCLUSIONS:

EVs were involved in the ATP7B-mediated mechanism underlying CDDP resistance. Further clarification of the EV-induced CDDP-resistance mechanism may lead to novel therapeutic strategies for HNSCC.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Benzylidene Compounds / Extracellular Vesicles / Head and Neck Neoplasms / Aniline Compounds / Antineoplastic Agents Limits: Humans Language: En Journal: Head Neck Journal subject: NEOPLASIAS Year: 2024 Type: Article Affiliation country: Japan
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Benzylidene Compounds / Extracellular Vesicles / Head and Neck Neoplasms / Aniline Compounds / Antineoplastic Agents Limits: Humans Language: En Journal: Head Neck Journal subject: NEOPLASIAS Year: 2024 Type: Article Affiliation country: Japan