RRC ID 37007
Author Shirako Y, Taya Y, Sato K, Chiba T, Imai K, Shimazu Y, Aoba T, Soeno Y.
Title Heterogeneous tumor stromal microenvironments of oral squamous cell carcinoma cells in tongue and nodal metastatic lesions in a xenograft mouse model.
Journal J. Oral Pathol. Med.
Abstract BACKGROUND:Oral squamous cell carcinoma exhibits a poor prognosis, caused by aggressive progression and early-stage metastasis to cervical lymph nodes. Here, we developed a xenograft mouse model to explore the heterogeneity of the tumor microenvironment that may govern local invasion and nodal metastasis of tumor cells.
METHODS:We transplanted five oral carcinoma cell lines into the tongues of nude mice and determined tongue tumor growth and micrometastatic dissemination by serially sectioning the tongue and lymph node lesions in combination with immunohistochemistry and computer-assisted image analysis. Our morphometric analysis enabled a quantitative assessment of blood and lymphatic endothelial densities in the intratumoral and host stromal regions.
RESULTS:All cell lines tested were tumorigenic in mouse tongue. The metastatic lesion-derived carcinoma cell lines (OSC19, OSC20, and HSC2) yielded a 100% nodal metastasis rate, whereas the primary tumor-derived cell lines (KOSC2 and HO-1-u-1) showed <40% metastatic potential. Immunohistochemistry showed that the individual cell lines gave rise to heterogeneous tumor architecture and phenotypes and that their micrometastatic lesions assimilated the immunophenotypic properties of the corresponding tongue tumors. Notably, OSC19 and OSC20 cells shared similar aggressive tumorigenicity in both the tongue and lymph node environments but displayed markedly diverse immunophenotypes and gene expression profiles.
CONCLUSIONS:Our model facilitated comparing the tumor microenvironments in tongue and lymph node lesions. The results support that tumorigenicity and tumor architecture in the host tongue environment depend on the origin and properties of the carcinoma cell lines and that metastatic progression may take place through heterogeneous tumor-host interactions.
Volume 44(9)
Pages 656-68
Published 2015-10
DOI 10.1111/jop.12318
PMID 25765182
MeSH Animals Carcinoma, Squamous Cell / pathology* Cell Line, Tumor Disease Models, Animal* Female Head and Neck Neoplasms / pathology* Heterografts Humans Image Processing, Computer-Assisted Immunohistochemistry Lymphatic Metastasis Mice Mice, Nude Neoplasm Micrometastasis Neoplasm Transplantation Phenotype Squamous Cell Carcinoma of Head and Neck Tongue Neoplasms / pathology* Transcriptome Tumor Cells, Cultured Tumor Microenvironment
IF 2.03
Times Cited 2
Human and Animal Cells HSC-2(RCB1945) HO-1-u-1(RCB2102)