A Human Thyroid Cancer Cell Line, DH-14-3, Newly Established from Poorly Differentiated Thyroid Carcinoma

Abstract

Poorly differentiated thyroid carcinoma (PDTC) is a newly recognized histological type of malignant thyroid tumor, accounting for about 2 -13% of all thyroid carcinomas. PDTC is considered as a morphologically and biologically intermediate stage between well-differentiated thyroid carcinoma and anaplastic thyroid carcinoma. PDTC preferentially manifests bone metastases. We here established a cell line from a resected tumor specimen from a 70-year-old male patient with PDTC who presented with multiple bone metastases. This new thyroid tumor cell line was designated as DH-14-3 and was subsequently grown in culture for several years. DH-14-3 cells express thyroglobulin in the cytoplasm and thyroid transcription factor-1 in the nuclei, both proteins of which are specific markers for the thyroid gland. Importantly, triiodothyronine (T3) was detected in the cultured medium of DH-14-3 cells, in which, however, thyroxine (T4) was undetectable. Moreover, DH-14-3 cells secreted interleukin-8, transforming growth factor-β1, vascular endothelial growth factor, matrix metalloproteinase-1 and parathyroid hormone-related protein, all of which may be responsible for the aggressiveness or bone metastasis of PDTC. Thus, the production of these proteins may reflect the metastatic potential of this cell line. DH-14-3 cells also express CXC chemokine receptor-4 and epidermal growth factor receptor, and carry a missense mutation in the p53 tumor suppressor gene. In fact, transplantation of DH-14-3 cells into the back of nude mice resulted in the formation of tumors, thereby confirming the capability of tumorigenesis. DH-14-3 cells may be useful for investigating the biological features of PDTC and will contribute to the therapeutic study of thyroid cancer.

Genome-wide expression analysis suggests a crucial role of dysregulation of matrix metalloproteinases pathway in undifferentiated thyroid carcinoma

“…Proteins encoded by MMP and MT-MMP genes can alter cell-cell and cell-ECM junctions; both mediate the release and activation of autocrine or paracrine signaling molecules such as angiogenic activators as well as activate or deactivate cell surface receptors, promoting invasiveness and metastasis [ 34 ]. On the other hand, matrix metalloproteinase-1 may be responsible for the aggressiveness or bone metastasis of poorly differentiated thyroid carcinoma [ 35 ].…”

The role of APE/Ref-1 signaling pathway in hepatocellular carcinoma progression

“…Furthermore, depletion of APE/Ref-1 also resulted in evident attenuation of cell invasiveness, possibly mediated by decreased activities of MMP-1 and Snail. MMP-1 was considered to be closely associated with tumor aggressiveness, metastatic potential and poor prognosis ( 26 – 29 ). Specifically, MMP-1 expression is largely controlled at the transcriptional level through a major enhancer element consisting of a consensus AP-1 site ( 30 – 32 ).…”

Chemokines and Bone

“…Among several genes to be upregulated by RET/PTC1-mediated transformation of human thyroid cells, CXCL8 (RNA and protein) was the main upregulated gene [176]. The poorly differentiated thyroid carcinoma cell lines SMP and DH-14-3 also have high constitutive levels of CXCL8 [177]. When Bauerle et al [178] examined a panel of thyroid cancer cell lines, they found those which secreted low levels of CXCL8 were not capable of forming tumors in vivo, while the two cell lines that were highly tumorigenic (BCPAP and 8505C) secreted much higher amounts of CXCL8.…”