Patient-derived spheroids and patient-derived organoids simulate evolutions of lung cancer
Surina,
Tanggis,
Tomoko Suzuki,
Shu Hisata,
Kazutaka Fujita,
Satomi Fujiwara,
Fangyuan Liu,
Noriyoshi Fukushima,
Takuji Suzuki,
Naoko Mato,
Koichi Hagiwara
Affiliations
Surina
Pulmonary Medicine, Cardiovascular and Pulmonary Diseases, Programs of Clinical and Community Medicine, Jichi Medical University Graduate School of Medicine, Tochigi, Japan
Tanggis
Division of Respiratory Medicine, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan
Tomoko Suzuki
Department of Pathology, Jichi Medical University Hospital, Tochigi, Japan
Shu Hisata
Pulmonary Medicine, Cardiovascular and Pulmonary Diseases, Programs of Clinical and Community Medicine, Jichi Medical University Graduate School of Medicine, Tochigi, Japan; Division of Respiratory Medicine, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan
Kazutaka Fujita
Division of Respiratory Medicine, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan
Satomi Fujiwara
Division of Respiratory Medicine, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan
Fangyuan Liu
Clinical Medical Research Center, The Affiliated Hospital, Inner Mongolia Medical University, Inner Mongolia, China
Noriyoshi Fukushima
Department of Pathology, Jichi Medical University Hospital, Tochigi, Japan
Takuji Suzuki
Pulmonary Medicine, Cardiovascular and Pulmonary Diseases, Programs of Clinical and Community Medicine, Jichi Medical University Graduate School of Medicine, Tochigi, Japan; Division of Respiratory Medicine, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan
Naoko Mato
Pulmonary Medicine, Cardiovascular and Pulmonary Diseases, Programs of Clinical and Community Medicine, Jichi Medical University Graduate School of Medicine, Tochigi, Japan; Division of Respiratory Medicine, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan
Koichi Hagiwara
Pulmonary Medicine, Cardiovascular and Pulmonary Diseases, Programs of Clinical and Community Medicine, Jichi Medical University Graduate School of Medicine, Tochigi, Japan; Division of Respiratory Medicine, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan; Corresponding author. Division of Respiratory Medicine, Department of Internal Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, 329-0498, Japan.
Cancer cells harbor many genetic mutations and gene expression profiles different from normal cells. Patient-derived cancer cells (PDCC) are preferred materials in cancer study. We established patient-derived spheroids (PDSs) and patient-derived organoids (PDOs) from PDCCs isolated from the malignant pleural effusion in 8 patients. The morphologies suggested that PDSs may be a model of local cancer extensions, while PDOs may be a model of distant cancer metastases. The gene expression profiles differed between PDSs and PDOs: Gene sets related to inflammatory responses and EMT were antithetically regulated in PDSs or in PDOs. PDSs demonstrated an attenuation of the pathways that contribute to the enhancement of transforming growth factor beta (TGF-β) induced epithelial mesenchymal transition (EMT), while PDOs demonstrated an attenuation of it. Taken together, PDSs and PDOs have differences in both the interaction to the immune systems and to the stroma. PDSs and PDOs will provide a model system that enable intimate investigation of the behavior of cancer cells in the body.
