Increased expression of S100A4 and its prognostic significance in esophageal squamous cell carcinoma

Ninomiya, Itasu; Ohta, Tetsuo; Fushida, Sachio; Endo, Yuichi; Hashimoto, Takeji; Yagi, Masao; Fujimura, Takashi; Nishimura, Genichi; Tani, Takashi; Shimizu, Kouichi; Yonemura, Yutaka; Heizmann, Claus W.; Schäfer, Beat W.; Sasaki, Takuma; Miwa, Koichi

doi:10.3892/ijo.18.4.715

Cited by 70 publications

(65 citation statements)

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“…Strong immunostaining was observed at the tumour invading front and metastatic site. This observation is further confirmed by quantitative real-time RT -PCR analysis, which shows higher S100A4 mRNA in lymph node metastasis as compared to primary tumours, supporting the role of S100A4 in cell motility and invasion (Ninomiya et al, 2001). Previous immunohistochemical studies of S100A4 showed an overexpres- sion in 41% of breast carcinomas (Rudland et al, 2000), 55% of gastric carcinomas (Yonemura et al, 2000), 94% of colorectal adenocarcinomas (Takenaga et al, 1997b), 93% of invasive pancreatic carcinomas (Rosty et al, 2002), and 25% of oesophageal squamous carcinoma.…”

Section: Analysis Of Thyroid Tumour Specimens For S100a4 Gene Expresssupporting

confidence: 60%

S100A4 (Mts1) gene overexpression is associated with invasion and metastasis of papillary thyroid carcinoma

et al. 2005

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Tumour cell invasion and metastasis are the hallmark of malignant neoplasm. S100A4 is a member of small calcium-binding protein family and is involved in the cell proliferation and cancer progression. S100A4 is capable of inducing metastasis in animal models and is associated with aggressive phenotype of human tumours. We previously identified S100A4 as a candidate gene involved in anaplastic thyroid cancer metastasis by microarray analysis. To further determine whether S100A4 overexpression is associated with thyroid tumour invasion and metastasis, in the present study, we examined S100A4 gene expression in six benign multinodular goitres (MNG) and 28 matched samples of adjacent normal thyroid tissue (N), primary (T) and metastatic (M) papillary thyroid carcinomas (PTC) by immunohistochemistry and real-time reverse transcription -polymerase chain reaction (RT-PCR) analysis. This gave us the advantage of directly comparing levels of S100A4 expression within the same genetic background. Using immunohistochemistry, we found that high levels of S100A4 were detected in 24 of 28 (86%) PTC specimens and their local regional lymph node or distant metastases. No S100A4 staining was observed in normal thyroid tissues and simple MNG. However, in MNG coexistent with PTC, moderate focal staining could be found in 11 of 15 MNG adjacent to PTC. The S100A4 was stained more intensely in invading fronts than in central portions of both T and M. Real-time RT -PCR analysis of primary tumours and their matched lymph node metastasis demonstrated that significantly higher S100A4 transcripts were present in metastatic tumours as compared to the primary tumours (Po0.01). These data suggest that overexpression of S100A4 is associated with thyroid tumour invasion and metastasis and it may be a potential target for therapeutic intervention.

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Section: Analysis Of Thyroid Tumour Specimens For S100a4 Gene Expresssupporting

confidence: 60%

S100A4 (Mts1) gene overexpression is associated with invasion and metastasis of papillary thyroid carcinoma

et al. 2005

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“…The presence of the EF-hand-containing calcium-binding protein S100A4 in carcinoma cells has been associated with a poor prognosis in patients with carcinomas of the bladder, colorectum, gall bladder, oesophagus and lung (Kimura et al, 2000;Ninomiya et al, 2001;Davies et al, 2002;Gongoll et al, 2002;Nakamura et al, 2002). In an archival set of 349 breast cancer patients, less than 20% of patients with S100A4 in their carcinoma cells were alive after 20 years, whereas greater than 90% of patients with less than 1% S100A4 positive carcinoma cells survived over the same period .…”

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confidence: 99%

Mutually antagonistic actions of S100A4 and S100A1 on normal and metastatic phenotypes

et al. 2004

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Increased levels of the homodimeric calcium-binding protein, S100A4, have been shown to cause a metastatic phenotype in at least three independent model systems of breast cancer and its presence in carcinoma cells has been shown to be associated with a reduction in the survival of patients suffering from a range of different cancers. S100A4 has been shown to interact in vitro with another member of the S100 family of proteins, S100A1. The purpose of the present study was to find out whether S100A1 could affect S100A4 function. Fluorescence resonance energy transfer was used to show the interaction of S100A4 and S100A1 in living cells and the binding affinities between S100A4 and S100A1 were determined using a biosensor. S100A1 reduced the S100A4 inhibition of nonmuscle myosin A self-association and phosphorylation in vitro. S100A1 reduced S100A4 induced motility and growth in soft agar and metastasis in vivo. The results show for the first time that interactions between different S100 proteins can affect cancer-related activity, and that the presence of S100A1 protein in carcinoma cells might modulate the effect of S100A4 on their metastatic abilities.

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“…Several studies have associated the S100A4 protein with increased metastatic capacity of cancer cells (Davies et al, 1993;Maelandsmo et al, 1996;Levett et al, 2002), and more recently a correlation between the level of S100A4 protein and prognostic outcome has been reported in various types of cancer (lung gall bladder, oesophageal, gastric, breast and colon) Rudland et al, 2000;Yonemura et al, 2000;Ninomiya et al, 2001;Gongoll et al, 2002;Nakamura et al, 2002). Several laboratories have studied the involvement of S100A4 in invasion and metastasis, but little is still understood of the mechanism by which it exerts the metastasis-promoting effects.…”

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confidence: 99%

Interferon-γ suppresses S100A4 transcription independently of apoptosis or cell cycle arrest

et al. 2003

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The S100A4 protein has been associated with increased metastatic capacity of cancer cells, and recent studies have suggested a correlation between the expression level of S100A4 and the prognostic outcome for patients with various types of cancer. The knowledge about the mechanisms underlying the metastasis-promoting effects is still limited, and the aim of the present study was to elucidate signal transduction pathways involved in the regulation of S100A4. After treatment of human carcinoma cells with interferon-gamma (IFN-g), we observed downregulation of S100A4 both at mRNA and protein levels. The effect was not dependent on IFN-g-induced apoptosis or IFN-g-mediated cell cycle arrest. Moreover, IFN-g-mediated decrease in mRNA stability could not account for the observed decrease in S100A4 transcript level. Finally, microarray analysis suggests ISGF3G, ETV5, ZNF133 and CEBPG as possible candidate genes involved in IFN-g-mediated repression of S100A4.

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Increased expression of S100A4 and its prognostic significance in esophageal squamous cell carcinoma

Cited by 70 publications

References 0 publications

S100A4 (Mts1) gene overexpression is associated with invasion and metastasis of papillary thyroid carcinoma

S100A4 (Mts1) gene overexpression is associated with invasion and metastasis of papillary thyroid carcinoma

Mutually antagonistic actions of S100A4 and S100A1 on normal and metastatic phenotypes

Interferon-γ suppresses S100A4 transcription independently of apoptosis or cell cycle arrest

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