Interleukin-10 induces TNF-driven apoptosis and ROS production in salivary gland cancer cells
Maksym Skrypnyk,
Tetiana Yatsenko,
Oleksandra Riabets,
Yousef Salama,
Margarita Skikevych,
Taro Osada,
Morikuni Tobita,
Satoshi Takahashi,
Koichi Hattori,
Beate Heissig
Affiliations
Maksym Skrypnyk
Department of Research Support Utilizing Bioresource Bank, Graduate School of Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
Tetiana Yatsenko
Department of Research Support Utilizing Bioresource Bank, Graduate School of Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
Oleksandra Riabets
Department of Research Support Utilizing Bioresource Bank, Graduate School of Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
Yousef Salama
An-Najah Center for Cancer and Stem Cell Research, Faculty of Medicine and Health Sciences, An-Najah National University, P.O. Box 7, Nablus 99900800, Palestine
Margarita Skikevych
Department of Surgical Dentistry and Maxillofacial Surgery with Plastic and Reconstructive Surgery of Head and Neck, Poltava State Medical University, 23 Shevchenko Street. Poltava, Ukraine
Taro Osada
Department of Gastroenterology Juntendo University Urayasu Hospital, Japan
Morikuni Tobita
Department of Oral and Maxillofacial Surgery, Juntendo University School of Medicine, Japan
Satoshi Takahashi
Division of Clinical Precision Research Platform, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
Koichi Hattori
Center for Genome and Regenerative Medicine, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan; Corresponding author.
Beate Heissig
Department of Research Support Utilizing Bioresource Bank, Graduate School of Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan; Corresponding author. Dep. of Research Support Utilizing Bioresource Bank Juntendo University, Graduate School of Medicine 2-1-1 Hongo, Bunkyo-ku Tokyo, 113-8421, Japan.
Treatment resistance after chemo-/immunotherapy occurs in patients with head and neck squamous cell cancers (HNSCs), including salivary gland cancers (SGCs). Interleukin-10 (IL-10), a cytokine with pro- and anti-cancer effects, has an unclear impact on HNSC/SGC cells. We show that HNSC patients exhibiting high expression of IL-10 and its receptor IL-10Rα experience have prolonged overall survival. Immunoreactive IL-10 was low in ductal cells of human SGC biopsies. Human (A253) and murine WR21-SGC cells expressed IL-10Rβ, but only A253 cells expressed IL-10 and IL-10Rα. The addition of recombinant IL-10 impaired SGC cell proliferation and induced apoptosis in vitro. N-acetylcysteine restored IL-10-induced reactive oxygen species (ROS) production but did not prevent IL-10-mediated viability loss. Mechanistically, recIL-10 delayed cell cycle progression from G0/G1 to the S phase with cyclin D downregulation and upregulation of NF-kB. IL-10 increased tumor necrosis factor-α (TNF-α) in A253 and WR21 and FasL in WR21 cells. Neutralizing antibodies against TNF-α and NF-kB inhibition restored SGC proliferation after IL-10 treatment, emphasizing the critical role of TNF-α and NF-kB in IL-10-mediated anti-tumor effects. These findings underscore the potential of IL-10 to impede SGC cell growth through apoptosis induction, unraveling potential therapeutic targets for intervention in salivary gland carcinomas.
