Establishment of lung cancer cell lines and tumorigenesis in mice from malignant pleural effusion in patients with lung cancer

Background: Lung cancer was often diagnosed by malignant pleural effusion (MPE). Excessive MPE is generally discarded. The establishment of cell lines and the generation of cancer mouse models have the potential to be directly linked to personalized medicine. This study aimed to establish cell lines and generate mouse models using MPE.

Methods: Cells derived from 5 mL of MPE were cultured in several conditions, including 100% MPE supernatant and Roswell Park Memorial Institute-1640 supplemented with 10% fetal bovine serum (FBS) or 10% MPE supernatant. When steady cell growth was observed, fewer cells were spread and the colonies were selected to establish the cell line. Cells derived from 10 mL of MPE were inoculated subcutaneously into non-obese diabetic-severe combined immunodeficiency (NOD-scid) and NOD.Cg-Prkdc^scid Il2rg^tmlWjl /SzJ (NSG) mice to assess tumorigenic potential.

Results: MPEs were obtained from 28 lung cancer patients, 23 of whom had adenocarcinoma. Cell lines were established from 5 patients (18%). Tumorigenesis was observed in 6 of 28 cases (21%). However, in 7 cases, the mice (7 NSG and 1 NOD-scid mice) became progressively weaker, lost their hair, and died within 12 weeks without tumorigenesis. The appearance and pathological findings were consistent with graft-versus-host disease. Cell line establishment and tumorigenesis in mice were associated with a lower response to first-line therapy and poorer prognosis of patients.

Conclusions: When MPEs were simply utilized, the cell line establishment rate was 18% and the engraftment rate in mice was 21%. The prognosis of patients who underwent cell line establishment and engraftment in mice was poor.