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Published on: May 25, 2018
An imageable metastatic treatment model of nasopharyngeal carcinoma
Tengfei Liu1, Yanqin Ding, Weibing Xie
1Cancer Institute, Nanfang Hospital, Southern Medical University, Key Laboratory of Transcriptomics and Proteomics of Human Diseases, Xiang-Ya School of Medicine, Central South University, Guangzhou, China.
Purpose:
Nasopharyngeal carcinoma is highly prevalent in southern China and is often resistant to current treatment options.
Experimental Design:
Clinically relevant mouse models are necessary for further understanding and drug discovery in this disease. Two nasopharyngeal carcinoma cell lines, stably expressing green fluorescent protein (GFP), 5-8F-GFP and 6-10B-GFP, were established. The cells were orthotopically injected into the nasopharynx or ectopically into the subcutis of nude mice. Whole-body fluorescence imaging was used to monitor the growth of the primary tumor as well as angiogenesis and metastasis.
Results:
The metastatic behavior of 5-8F and 6-10B were distinct in the orthotopic model. Orthotopic implantation of highly metastatic 5-8F cells resulted in brain invasion, cervical lymph node metastases, and pulmonary metastases similar to what is often observed in patients. Cell line 6-10B was less metastatic, which occasionally resulted in pulmonary metastasis. GFP enabled imaging of micrometastasis. Neither 5-8F nor 6-10B were metastatic in the s.c. site. These results indicated that, in addition to the cancer cell type, the host microenvironment was critical for metastasis to occur consistent with the "seed-and-soil" hypothesis. 5-8F was highly sensitive to 5-fluorouracil (5-FU), whereas 6-10B was moderately sensitive.
Conclusions:
The imageable orthotopic model should play a critical role in elucidating the mechanisms involved in the growth, progression, metastasis, and angiogenesis of nasopharyngeal carcinoma and for evaluation of novel compounds with potential efficacy.
Insights
This study developed imageable mouse models for nasopharyngeal carcinoma, revealing distinct metastatic patterns and drug sensitivities. These models are crucial for understanding cancer progression and testing new treatments.
Area of Science:
- Oncology
- Cancer Biology
- Translational Research
Background:
- Nasopharyngeal carcinoma (NPC) is prevalent in southern China and exhibits resistance to existing therapies.
- Development of clinically relevant preclinical models is essential for advancing NPC research and drug discovery.
Purpose of the Study:
- To establish and characterize imageable orthotopic mouse models for nasopharyngeal carcinoma (NPC).
- To investigate the metastatic potential and drug sensitivity of distinct NPC cell lines in vivo.
- To evaluate the role of the host microenvironment in NPC metastasis.
Main Methods:
- Two nasopharyngeal carcinoma cell lines (5-8F and 6-10B) were engineered to express green fluorescent protein (GFP).
- Cells were orthotopically implanted into the nasopharynx or ectopically into the subcutis of nude mice.
- Whole-body fluorescence imaging was employed to monitor tumor growth, angiogenesis, and metastasis.
- The metastatic behavior and response to 5-fluorouracil (5-FU) were assessed.
Main Results:
- Orthotopic implantation of 5-8F cells led to significant brain, lymph node, and lung metastases, mirroring human disease.
- The 6-10B cell line exhibited lower metastatic potential, with occasional lung metastasis.
- GFP imaging allowed visualization of micrometastasis.
- Metastasis was dependent on both cancer cell type and host microenvironment, supporting the 'seed-and-soil' hypothesis.
- 5-8F cells showed high sensitivity to 5-FU, while 6-10B cells demonstrated moderate sensitivity.
Conclusions:
- The developed imageable orthotopic NPC models are valuable tools for studying tumor growth, metastasis, and angiogenesis.
- These models will facilitate the evaluation of novel therapeutic compounds for nasopharyngeal carcinoma.
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