Comparison of animal models for head and neck cancer cachexia.
OBJECTIVE
Despite its negative impact on cancer patients, there are few animal models of cancer cachexia. Our hypothesis was that different human cell lines would variably induce cachexia.


METHODS
Prospective animal study.


METHODS
We established two xenograft models in athymic mice and compared these with a cachexigenic cell line, the murine adenocarcinoma 16 (MAC16) cell line. Eight-week-old female, athymic mice were injected with human head and neck cell lines (JHU022, JHU012) and the MAC16 cell line. Body weight, food intake, body composition, leg weights, serum cytokines, and lipid mobilizing factor (LMF) were compared.


RESULTS
Mean food intake for all groups was equivalent. Mean percent change in body weight after 18 days was 18%, 19%, 12%, and 3% for control, JHU012, JHU022, and MAC16 experimental groups, respectively. Both JHU022- and MAC16-injected mice showed wasting even when tumor burden was low. In contrast, mice injected with JHU012 developed larger tumors yet lacked evidence of cachexia. These mice demonstrated loss of lean body mass but not fat mass. Serum cytokine levels for interleukin (IL)-1 alpha and IL-1 beta were elevated in JHU022-bearing mice, whereas IL-1 alpha, IL-6, interferon (IFN)-gamma, and tumor necrosis factor alpha (TNF)-alpha were elevated in MAC16-bearing mice. LMF was present in both the JHU022 and JHU012 cell lines.


CONCLUSIONS
The JHU022 cell line caused more severe cachexia than the JHU012 cells, suggesting these cell lines may be used to further study cancer cachexia. IL-1 alpha and IL-1 beta in the JHU022 model may be mediators of cachexia, whereas TNF-alpha, IFN-gamma, and IL-6 may be mediators in MAC16-induced cachexia.
Cannon
Trinitia
T
Department of Otolaryngology-Head and Neck Surgery, University of North Carolina School of Medicine, Chapel Hill, North Carolina, NC, USA.
Couch
Marion
M
Yin
Xiaoying
X
Guttridge
Denis
D
Lai
Victor
V
Shores
Carol
C
D000230:Adenocarcinoma / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D001823:Body Composition; D002100:Cachexia / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D018450:Disease Progression; D005260:Female; D006258:Head and Neck Neoplasms / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental; D014183:Transplantation, Heterologous
D016207:Cytokines; D009363:Neoplasm Proteins