Figure 5. THJ-11T thyrosphere-derived cells are tumorigenic and metastasize more aggressively than parental monolayer-derived cells in an orthotopic mouse model of thyroid carcinoma.

(A) One representative experiment showing the location of the thyroid gland and trachea. (B) Orthotopic tumors generated with 500,000 parental monolayer-derived cells and 10,000 thyrosphere-derived cells. H&E staining revealed the invasion of anaplastic tumors into the thyroid gland, trachea, smooth muscle and esophagus. F, normal thyroid follicles; S, smooth muscle; asterisk, thyroid tumors; E, esophagus. (C) Orthotopic tumors arising from thyrosphere-derived cells had a larger tumor volume than did those arising from parental monolayer-derived cells (60 ± 30 mm³ versus 40 ± 20 mm³; P = 0.25). (D) Immunohistochemical staining of ALDH, CD44, CXCR4 and CD133 in orthotopic tumors generated from monolayer- and thyrosphere-derived cells. Note the intense immunoreactivity of ALDH, CD44 and CXCR4 in thyrosphere-derived tumors four weeks post-injection. (E) Schematic representation of lung colonization assay by tail-vein injection model. Representative histology images of mice with lung metastasis induced by THJ-11T monolayer cells. Note that mice injected with thyrosphere-derived cells did not develop lung metastasis. Scale bar, 100 µm.