Microarray Analysis of Metastasis-Associated Gene Expression Profiling in a Murine Model of Thyroid Carcinoma Pulmonary Metastasis: Identification of S100A4 (Mts1) Gene Overexpression as a Poor Prognostic Marker for Thyroid Carcinoma

• Published in: The journal of clinical endocrinology and metabolism Vol. 89; no. 12; pp. 6146 - 6154
• Main Authors: Zou, Minjing, Famulski, Konrad S., Parhar, Ranjit S., Baitei, Essa, Al-Mohanna, Futwan A., Farid, Nadir R., Shi, Yufei
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.12.2004; Copyright by The Endocrine Society
• Subjects: Animals; Biological and medical sciences; Biomarkers; Blotting, Northern; Carcinoma - genetics; Carcinoma - secondary; Cell Line, Tumor; Computer Systems; Endocrinopathies; Female; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene Expression Profiling; Genes, p16; Humans; Lung Neoplasms - genetics; Lung Neoplasms - secondary; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Nude; Microarray Analysis; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; Thyroid Neoplasms - pathology; Thyroid. Thyroid axis (diseases); Vertebrates: endocrinology; Endocrinopathy; Animal model; Prognosis; Respiratory disease; Thyroid diseases; DNA chip; Biological marker; Gene overexpression; Malignant tumor; Gene expression profile; Thyroid cancer; Lung metastasis; Endocrinology; Tumor suppressor gene
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2004-0418

Tumor cell invasion and metastasis are the hallmark of malignant neoplasm. Despite advances in the management of thyroid carcinoma and other solid tumors, metastasis continues to be the most significant cause in cancer mortality. To gain new insights into this complex process in thyroid carcinoma, we established a thyroid carcinoma cell line (ARO-met2) with high metastatic capacity to the lung by sequential passage of a human anaplastic thyroid cancer cell line (ARO) through the lung of a nude mouse. Global patterns of gene expression were analyzed in cells of the parental ARO and the ARO-met2, using Atlas human cancer 1.2 array with 1176 cancer-related genes. In total, 184 genes were differentially expressed more than 1.5 times, and 64 genes were differentially expressed over two times. Among those 64 genes, 43 were overexpressed, and 21 genes were underexpressed. Many genes whose increased expression was thought to be related to tumor progression were identified, such as c-Met, ezrin, integrin, motility-related protein-1, cadherin, and S100A4. The most highly expressed gene is the S100A4 (8-fold higher than control), which is a member of a small calcium binding protein family and is involved in the cell proliferation and cancer progression. The S100A4 overexpression in the ARO-met2 cells was later confirmed by Northern blot and real-time reverse transcriptase-PCR. Analysis of 49 thyroid tumor specimens by real-time reverse transcriptase-PCR (eight benign goiters, 36 papillary, and five anaplastic carcinomas) revealed that S100A4 overexpression was present in most advanced thyroid carcinomas and lymph node metastases, and was associated with poor prognosis. None of the benign goiters was found to have S100A4 overexpression. These data suggest that S100A4 could be used as a prognostic marker for thyroid carcinoma. Given that S100A4 is involved in tumor progression and metastasis, it may be a potential target for therapeutic intervention.