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

doi:10.1016/j.heliyon.2023.e13829

Patient-derived spheroids and patient-derived organoids simulate evolutions of lung cancer

Heliyon. 2023 Feb 18;9(3):e13829. doi: 10.1016/j.heliyon.2023.e13829. eCollection 2023 Mar.

Authors

Surina¹, Tanggis², Tomoko Suzuki³, Shu Hisata^{1

2}, Kazutaka Fujita², Satomi Fujiwara², Fangyuan Liu⁴, Noriyoshi Fukushima³, Takuji Suzuki^{1

2}, Naoko Mato^{1

2}, Koichi Hagiwara^{1

2}

Affiliations

¹ Pulmonary Medicine, Cardiovascular and Pulmonary Diseases, Programs of Clinical and Community Medicine, Jichi Medical University Graduate School of Medicine, Tochigi, Japan.
² Division of Respiratory Medicine, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan.
³ Department of Pathology, Jichi Medical University Hospital, Tochigi, Japan.
⁴ Clinical Medical Research Center, The Affiliated Hospital, Inner Mongolia Medical University, Inner Mongolia, China.

Abstract

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.

Keywords: Extracellular matrix; Immune system; Lung cancer; Organoid; Spheroid.