An imageable metastatic treatment model of nasopharyngeal carcinoma.
OBJECTIVE
Nasopharyngeal carcinoma is highly prevalent in southern China and is often resistant to current treatment options.


METHODS
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.
Liu
Tengfei
T
Cancer 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.
Ding
Yanqin
Y
Xie
Weibing
W
Li
Zuguo
Z
Bai
Xiaoyan
X
Li
Xin
X
Fang
Weiyi
W
Ren
Caiping
C
Wang
Shuang
S
Hoffman
Robert M
RM
Yao
Kaitai
K
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002277:Carcinoma / Q000473:pathology* / Q000628:therapy*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D008953:Models, Anatomic; D009303:Nasopharyngeal Neoplasms / Q000473:pathology* / Q000628:therapy*; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic
D000970:Antineoplastic Agents; D049452:Green Fluorescent Proteins