Human-in-mouse modeling of primary head and neck squamous cell carcinoma.
OBJECTIVE
To develop a reliable modeling system for head and neck squamous cell carcinoma (HNSCC).


METHODS
Laboratory-based translational study.


METHODS
HNSCC tissue was obtained from patients at biopsy/resection, cultured, and implanted into mice. In vivo, tumor growth, and survival was monitored by bioluminescence imaging. Histology and immunohistochemistry (IHC) were used to confirm HNSCC and human origin.


RESULTS
Short-term culture techniques were optimized allowing survival of primary HNSCC cells more than 7 days in 76% of tumors. The size of the tumor biopsy collected did not correlate with the success of short-term culture or xenograft establishment. Xenograft modeling was attempted in primary HNSCCs from 12 patients with a success rate of 92%. Immunostaining confirmed human origin of epithelial tumor cells within the modeled tumor. Bioluminescence and Ki67 IHC suggested tumor proliferation within the model. Luciferase expression was maintained for as long as 100 days in modeled tumors.


CONCLUSIONS
The techniques developed for short-term primary tumor culture followed by xenograft modeling provide a low-cost and tractable model for evaluation of HNSCC response to standard and novel therapies. The high success rate of human-in-mouse tumor formation from primary HNSCC suggests that selection pressures for tumor growth in this model may be less than those observed for establishment of cell lines. Bioluminescent imaging provides a useful tool for evaluating tumor growth and could be expanded to measure response of the modeled tumor to therapy. This model could be adapted for xenograft modeled growth of other primary tumor types.
Law
Jonathan H
JH
Department of Otolaryngology , Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Whigham
Amy S
AS
Wirth
Pamela S
PS
Liu
Dan
D
Pham
Michelle Q
MQ
Vadivelu
Sangeetha
S
Kirkbride
Kellye C
KC
Brown
Brandee T
BT
Burkey
Brian B
BB
Sinard
Robert J
RJ
Netterville
James L
JL
Yarbrough
Wendell G
WG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D006258:Head and Neck Neoplasms / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000473:pathology*; D051381:Rats; D014132:Trachea / Q000166:cytology / Q000637:transplantation; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured