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. Author manuscript; available in PMC: 2012 Nov 15.
Published in final edited form as: Cancer Res. 2011 Oct 5;71(22):7103–7112. doi: 10.1158/0008-5472.CAN-10-3192

Figure 6. Inhibition of mTOR with rapamycin and RAD001 prevents the metastatic spread of primary HNSCC lesions to cervical lymph nodes, extending animal survival.

Figure 6

A. Patterns of tumor regression in rapamycin- and RAD001-treated UMSCC2 HNSCC xenograft. After rapamycin treatment, the remnant tumor has become lobulated, with blocks of neoplastic cells divided by dense collagen strands. Similar results were observed in RAD001 treated animals (not shown). In the hematoxylin-eosin stained tissue (inset) the collagen is evident by an increase in eosinophilic material between the cells. The small pictures on the right are higher magnification of the areas depicted as dotted squares, showing two stages in rapamycin-induced regression within the same slide. On top, apoptotic images can be identified within the tumoral mass (arrow heads). In the bottom, intercellular edema and hemorrhages are evident. B–D. The increase in blue-stained collagen bands is evident in the rapamycin and RAD001 treated animal (C and D, respectively) as compared with the vehicle treated mouse (B). Masson trichrome staining. E. Microvessel quantification in primary HNSCC tumors immunoreacted with CD31 and LYVE 1. There were no significant differences in CD31 expression between vehicle controls and rapamycin or RAD001 treated tumors. Rapamycin and RAD001 administration induced a significant decrease of lymphatic vessels density specifically within the tumor area, as judged by LYVE 1 staining (*** p<0.001). F. Percentage of metastatic lymph nodes in each animal in the vehicle- and rapamycin-treated groups. Rapamycin and RAD001 treatments induced a significant decrease the metastatic burden (*** p<0.001, ** p<0.01). G. Survival curve of mice carrying UMSCC2 HNSCC orthotopic xenografts treated with vehicle (n=26), rapamycin (n=20), and RAD001 (n=20). Treatment was started 10 days after HNSCC cell tongue implantation, when visible tumors were evident. As seen, all rapamycin and RAD001 treated animals were alive at the end of the study, while by contrast all animals in the vehicle-treated group succumbed to disease (*** p<0.001).