RRC ID 80995
Author Suzuki M, Kobayashi H, Hara D, Hanaoka H.
Title Elimination of radiation-induced senescent cancer cells and stromal cells in vitro by near-infrared photoimmunotherapy.
Journal Cancer Med
Abstract INTRODUCTION:Therapy-induced senescent cancer and stromal cells secrete cytokines and growth factors to promote tumor progression. Therefore, senescent cells may be novel targets for tumor treatment. Near-infrared photoimmunotherapy (NIR-PIT) is a highly tumor-selective therapy that employs conjugates of a molecular-targeting antibody and photoabsorber. Thus, NIR-PIT has the potential to be applied as a novel senolytic therapy. This study aims to investigate the efficacy of NIR-PIT treatment on senescent cancer and stromal cells.
METHODS:Two cancer cell lines (human lung adenocarcinoma A549 cells and human pancreatic cancer MIA PaCa-2 cells) and two normal cell lines (mouse fibroblast transfected with human epidermal growth factor receptor 2 [HER2] cells and human fibroblast WI38 cells) were used. The cytotoxicity of NIR-PIT was evaluated using anti-epidermal growth factor receptor (EGFR) antibody panitumumab and anti-HER2 antibody transtuzumab.
RESULTS:Cellular senescence was induced in A549 and MIA PaCa-2 cells by 10 Gy γ-irradiation. The up-regulation of cellular senescence markers and characteristic morphological changes in senescent cells, including enlargement, flattening, and multinucleation, were observed in cancer cells after 5 days of γ-irradiation. Then, NIR-PIT targeting EGFR was performed on these senescent cancer cells. The NIR-PIT induced morphological changes, including bleb formation, swelling, and the inflow of extracellular fluid, and induced a significant decrease in cellular viability. These results suggested that NIR-PIT may induce cytotoxicity using the same mechanism in senescent cancer cells. In addition, similar morphological changes were also induced in radiation-induced senescent 3T3-HER2 fibroblasts by NIR-PIT targeting human epidermal growth factor receptor 2.
CONCLUSION:NIR-PIT eliminates both senescent cancer and stromal cells in vitro suggesting it may be a novel strategy for tumor treatment.
Volume 13(12)
Pages e7381
Published 2024-6-1
DOI 10.1002/cam4.7381
PMID 38888415
PMC PMC11184651
MeSH A549 Cells Animals Cell Line, Tumor Cellular Senescence* / radiation effects ErbB Receptors* / metabolism Gamma Rays Humans Immunotherapy* / methods Infrared Rays / therapeutic use Lung Neoplasms / pathology Lung Neoplasms / therapy Mice Panitumumab / pharmacology Phototherapy* / methods Receptor, ErbB-2 / metabolism Stromal Cells* / metabolism Trastuzumab / pharmacology
Human and Animal Cells WI-38(RCB0702) A549(RCB0098)