Anaplastic thyroid cancer (ATC) is a locally aggressive type of thyroid tumor with high rate of distant metastases. It is often incurable because it does not respond to radioiodine, radiotherapy, or chemotherapy. With conventional treatment, the median survival is about 6 months; therefore, new treatment options are needed. S100A4 is a calcium-binding protein related to the metastatic potential of carcinoma. Previous study has found S100A4 was overexpressed in human papillary thyroid carcinomas (PTC) tissues, and overexpression of S100A4 is associated with thyroid tumour invasion and metastasis. In the present study, we first examined S100A4 protein expression in 14 ATC tissues, 20 PTC tissues and 14 normal thyroid tissue by immunohistochemistry analysis. We then knocked down of S100A4 expression by RNA interference (S100A4 siRNA) and investigated its effects on growth and metastasis in two human ATC cell lines 8505C (BRAFV600E) and Cal-62 (BRAFwt) in vitro and in vivo. S100A4 and BRAFV600E protein expression was evaluated by western blot assay and immunohistochemistry analysis. Using immunohistochemistry, we found that high levels of S100A4 were detected in ATC specimens and PTC specimens. No S100A4 staining was observed in normal thyroid tissues. S100A4 siRNA significantly decreased proliferation and increased apoptosis, and inhibited the invasive potential of the two cells in vitro. In addition, S100A4 siRNA could effectively inhibit BRAFV600E expression in the 8505C cells, and treatment with 100 ng/ml human recombinant BRAF V600E in S100A4 siRNA/8505C cells could partly restore its proliferative and invasive ability. Results of implantation in vivo showed S100A4 shRNA could significantly inhibit abdominal cavity metastasis and tumor growth in vivo. Furthermore, knockdown of S100A4 has significant role on invasion, metastasis and growth inhibition in the 8505C cells than that of in the Cal-62 cells. These results support the hypothesis that S100A4 contributes significantly to growth and metastasis, and that down-regulation of S100A4 expression decreases the metastatic potential of ATC cells. Furthermore, down-regulation of S100A4 expression is more marked in BRAFV600E cells than that of in the BRAFwt cells.

Lymphadenopathy is associated with a wide range of disorders; however, metastatic lymph nodes of malignancies are the most common cause for enlarged lymph nodes.

BackgroundThe transforming growth factor-beta (TGF-β) signaling pathway plays a critical role in promoting tumor growth. TGF-β1was found to be overexpressed in anaplastic thyroid cancer (ATC). We therefore tested our hypothesis that targeting TGF-β1 inhibits tumorigenesis of ATC cells.Material/MethodsEffects of TGF-β1 stimulation or TGF-β1 inhibition by small interfering RNA (TGF-β1siRNA) on proliferation, colony formation, and apoptosis in 8505C cells in vitro was detected using siRNAs and inhibitors to examine the TGF-β1 signaling pathway. A subcutaneously implanted tumor model of 8505C cells in nude mice was used to assess the effects of TGF-β1 inhibition on tumorigenesis development.ResultsTGF-β1siRNAs decreased proliferation and colony formation, and increased apoptosis in 8505C cells in vitro and inhibited tumor growth in vivo. TGF-β1siRNA inhibited phosphorylation ERK1/2 (pERK1/2) and increased p65-dependant PUMA mRNA and protein expression. Knockdown of p65 or PUMA by siRNA reduced TGF-β1siRNA-induced apoptosis, as well as caspase-3 and PARP activation. Upregulation of p65 or PUMA expression by TGF-β1siRNA requires pERK1/2 inhibition. TGF-β1 shRNA inhibited tumor growth in vivo.ConclusionsTherapies targeting the TGF-β1 pathway may be more effective to prevent primary tumor formation. The ability of this therapy to decrease tumorigenesis may be related to ERK1/2/NF-κB/PUMA signaling.

Pancreatic carcinoma is one of the most malignant and aggressive cancers. Increased motility and invasiveness of pancreatic cancer cells are believed to be associated with epithelial-to-mesenchymal transition (EMT). However, the molecular basis of EMT in pancreatic cancer cells is poorly understood. In this study, we examined the relationship between Jun dimerization protein 2 (JDP2), which is an AP-1 inhibitor, and EMT in human pancreatic carcinoma cells. We demonstrated that transforming growth factor-β1 (TGF-β1) promoted epidermal growth factor (EGF)-induced EMT in co-treated human pancreatic BxPC3 cells and that JDP2 overexpression reversed the EMT that was induced by co-treatment with TGF-β1 and EGF. These results suggest that EGF plays a principal role in EMT through its association with TGF-β1 in human pancreatic BxPC3 cells and that JDP2 may be a molecular target for pancreatic carcinoma intervention.