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P1.02 - Biology/Pathology (ID 614)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
P1.02-015 - Comparison of Study Models of Lung Cancer (ID 9318)
09:30 - 16:00 | Presenting Author(s): Yoshito Yamada
Lung cancer is the most prominent cancer in human with high mortality rate. Although chemo-radiation therapies have been improved, the patient survival is still poor. Thus, not only developing therapeutic medications, but also biomarkers of early diagnosis have been desired. Several models of primary lung cancer research are in use, however, systematic evaluation and characterization of models are required to have suitability and relevance based on study aims. To provide research environment for lung cancer, we reappraise relevant models for lung cancer.
Three concepts of primary lung cancer models were evaluated: (I) Urethane induced lung tumor. (II) Cell line induced tumor model via intravenous (iv) or subcutaneous (sc) injection. (III) ex vivo 3D primary cell culture model. 20 weeks after urethane injection, the animals were harvested to analyze tumor incidence and tumor immunity. Lewis Lung Carcinoma (LLC) cell line was employed for the orthotopic development of lung tumor in 2 weeks after the injection. Hanging drop method was used for the 3D culture of primary cells from LLC sc induced tumor. Immunohistochemistry (IHC) of proliferation markers (pH3 and Ki67), tumor immunity (CD4, CD8, B220, F4/80, NKp46, and PDL-1) were performed for a finer characterization of tumors.
Urethane and iv injection of LLC cell line developed heterogeneously distributed tumors in lung. sc injection stably developed single tumor nodule. 3D cultured primary cells formed spheroids within 5 days. IHC revealed that all tumors were consistently proliferating with less extend in urethane and 3D model. F4/80[+ ]cells and CD4[+] cells infiltrated into tumors significantly more than CD8[+], B220[+], or NKp46[+] cells. T cell populations (CD4[+] and CD8[+]) were much more prominent in LLC iv model than other models. Interestingly the expression of PDL-1 was found only in 3D model.
The urethane-induced primary lung tumor is reliable with a high rate of development, but needs longer time period to develop tumor compared to iv and sc models. iv injection model develops lung tumor in the original location. With relatively more convenience, sc model allows the analysis of tumor without adjacent tissue bias. 3D primary cell culture model enable for conferring characterization of individual tumor and strategic design of therapy, namely personalized medicine. The involvement and characteristics of immune cells found within tumors were comparable across all models. Injections by i.v. or s.c. of cell line to mouse can be considered as an alternative yet convenient model to develop various different types of lung cancers.