Related Experiment Video
Updated: May 15, 2026
Orthotopic Transplantation of Syngeneic Lung Adenocarcinoma Cells to Study PD-L1 Expression
Published on: January 19, 2019
Evaluation of novel orthotopic nude mouse models for human small-cell lung cancer
Takeshi Isobe1, Amir Onn, Daniel Morgensztern
1Department of Thoracic and Head and Neck Medical Oncology, Sheba Medical Center, Sheba, Israel.
Introduction:
Although subcutaneous xenograft models have been widely used to evaluate the antitumor activity of new compounds, these models present a major disadvantage because the tumors do not accurately represent the cancer biology, especially with regard to metastasis and drug sensitivity. Effective murine models of small-cell lung cancer (SCLC) are needed.
Methods:
To provide strategies for studying new therapies and tumor biology, we developed three orthotopic models of human SCLC (H69A, a variant of the National Cancer Institute [NCI]-H69 cell line selected for invasiveness in vitro, NCI-H187, and NCI-N417) in nude mice. Tumor cells were injected into their lungs and new cell lines were established from these tumors (H69ALu, H187Lu, and N417Lu) to select for a reproducible tumor growth pattern and minimize variations in tumor size.
Results:
In all three models tumors started as a solitary mass in the left lung and spread to mediastinal and axillary lymph nodes and to the right lung in a pattern similar to that observed in human SCLC. To test the accuracy of this model in representing SCLC as seen in the clinic, we compared the efficacy of chemotherapeutic agents in each model. Irinotecan significantly inhibited the growth and progression of all three human SCLC tumors, and cisplatin, paclitaxel, and etoposide significantly inhibited the growth and progression of H69ALu tumors over the control agent.
Conclusions:
We have established three orthotopic murine models of human SCLC closely resembling the course of human SCLC seen in the clinic including metastasis to lymph nodes and distant organs. They provide a means for better understanding the biology of this disease and will enable evaluation of novel therapeutic strategies.
Insights
New orthotopic models of human small-cell lung cancer (SCLC) in mice accurately mimic human disease progression and metastasis. These models enable better evaluation of novel SCLC therapies and drug sensitivity.
Area of Science:
- Oncology
- Preclinical Cancer Models
- Translational Research
Background:
- Subcutaneous xenograft models inadequately represent small-cell lung cancer (SCLC) biology, particularly metastasis and drug sensitivity.
- There is a critical need for effective murine models of SCLC.
Purpose of the Study:
- To develop and characterize orthotopic murine models of human SCLC.
- To establish models that accurately reflect SCLC tumor growth, metastasis, and drug response for preclinical studies.
Main Methods:
- Three human SCLC cell lines (H69A, NCI-H187, NCI-N417) were injected orthotopically into the lungs of nude mice.
- New cell lines (H69ALu, H187Lu, N417Lu) were established from these tumors to ensure reproducible growth patterns.
- The efficacy of chemotherapeutic agents was evaluated in these models.
Main Results:
- Orthotopic models demonstrated tumor growth originating in the left lung with metastasis to lymph nodes and the contralateral lung, mirroring human SCLC.
- Irinotecan significantly inhibited tumor growth across all three models.
- Cisplatin, paclitaxel, and etoposide showed significant inhibition of H69ALu tumor growth.
Conclusions:
- Three orthotopic murine models of human SCLC have been successfully established.
- These models closely mimic human SCLC clinical presentation, including metastasis.
- The models offer a valuable platform for understanding SCLC biology and evaluating new therapeutic strategies.
