Induction of S100A4 gene expression inhibits in vitro invasiveness of human squamous cell carcinoma, KOSC-3 cells

Uozumi, Masaki; Murao, Shinichi; Katayama, Naoya; Kitazawa, Sohei; Amatsu, Mutsuo; Maeda, Sakan

doi:10.1016/s0304-3835(99)00352-3

Cited by 9 publications

(8 citation statements)

References 22 publications

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“…VMR-Liv-Tet-on-S100A4 cells were grown in the absence (lanes 3-6) or presence of DOX for 24 h (lanes 7-10) and 48 h (lanes [11][12][13][14]. Lanes 1,5,9, and 13, anti-S100A4 rabbit antibodies; lanes 2, 4, 8, and 12, anti-non-muscle MHC IgG; lanes 3, 7, and 11, negative control, rabbit Ig; lanes 6, 10, and 14, negative control, no antibodies.…”

Section: Methodsmentioning

confidence: 99%

Liprin β1, a Member of the Family of LAR Transmembrane Tyrosine Phosphatase-interacting Proteins, Is a New Target for the Metastasis-associated Protein S100A4 (Mts1)

Kriajevska

Fischer-Larsen

Moertz³

et al. 2002

Journal of Biological Chemistry

124

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Metastasis-associated protein S100A4 (Mts1) induces invasiveness of primary tumors and promotes metastasis. S100A4 belongs to the family of small calcium-binding S100 proteins that are involved in different cellular processes as transducers of calcium signal. S100A4 modulates properties of tumor cells via interaction with its intracellular targets, heavy chain of non-muscle myosin and p53. Here we report identification of a new molecular target of the S100A4 protein, liprin ␤1. Liprin ␤1 belongs to the family of leukocyte common antigen-related (LAR) transmembrane tyrosine phosphatase-interacting proteins that may regulate LAR protein properties via interaction with another member of the family, liprin ␣1. We showed by the immunoprecipitation analysis that S100A4 interacts specifically with liprin ␤1 in vivo. Immunofluorescence staining demonstrated the co-localization of S100A4 and liprin ␤1 in the cytoplasm and particularly at the protrusion sites of the plasma membrane. We mapped the S100A4 binding site at the C terminus of the liprin ␤1 molecule between amino acid residues 938 and 1005. The S100A4-binding region contains two putative phosphorylation sites by protein kinase C and protein kinase CK2. S100A4-liprin ␤1 interaction resulted in the inhibition of liprin ␤1 phosphorylation by both kinases in vitro.Metastasis-associated protein S100A4 is highly expressed in metastatic tumors and tumor cell lines of different origins, and its expression is tightly associated with poor prognosis in cancer patients (1-6). The direct involvement of S100A4 in the formation of metastases has been shown in transgenic models, where the murine mammary tumor virus-S100A4 transgene provoked malignant progression of mammary tumors in mice (7,8).Different attempts have been made to elucidate the mechanisms underlying the role of S100A4 in tumor progression. Modulating the expression level of S100A4 in numerous tumor cell lines revealed its direct role in cell motility, invasiveness,

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Section: Methodsmentioning

confidence: 99%

Liprin β1, a Member of the Family of LAR Transmembrane Tyrosine Phosphatase-interacting Proteins, Is a New Target for the Metastasis-associated Protein S100A4 (Mts1)

Kriajevska

Fischer-Larsen

Moertz³

et al. 2002

Journal of Biological Chemistry

124

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“…The S100A4 gene was originally isolated as a gene differentially expressed in highly metastatic mouse mammary adenocarcinoma cells (Ebralidze et al, 1989). Introduction of the S100A4 gene into nonmetastatic tumor cell lines and suppression of its activity in metastatic ones proved its involvement in metastasis formation Maelandsmo et al, 1996;Takenaga et al, 1997;Lloyd et al, 1998;Uozumi et al, 2000). Stimulation of tumor metastasis was demonstrated in two transgenic mouse models with overexpression of the S100A4 gene Davies et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Extracellular S100A4(mts1) stimulates invasive growth of mouse endothelial cells and modulates MMP-13 matrix metalloproteinase activity

et al. 2004

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S100A4(mts1) protein expression has been strongly associated with metastatic tumor progression. It has been suggested as a prognostic marker for a number of human cancers. It is proposed that extracellular S100A4 accelerates cancer progression by stimulating the motility of endothelial cells, thereby promoting angiogenesis. Here we show that in 3D culture mouse endothelial cells (SVEC 4-10) respond to recombinant S100A4 by stimulating invasive growth of capillary-like structures. The outgrowth is not dependent on the stimulation of cell proliferation, but rather correlates with the transcriptional modulation of genes involved in the proteolytic degradation of extracellular matrix (ECM). Treatment of SVEC 4-10 with the S100A4 protein leads to the transcriptional activation of collagenase 3 (MMP-13) mRNA followed by subsequent release of the protein from the cells. b-Casein zymography demonstrates enhancement of proteolytic activity associated with MMP-13. This observation indicates that extracellular S100A4 stimulates the production of ECM degrading enzymes from endothelial cells, thereby stimulating the remodeling of ECM. This could explain the angiogenic and metastasis-stimulating activity of S100A4(mts1).

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“…This molecule has been linked to increased metastasis; its expression levels strongly correlate with the invasive and metastatic behavior of cultured tumor cells (4)(5)(6)8). In addition, S100A4 expression correlated with lymph node metastasis and prognosis in clinical studies of multiple cancers (7)(8)(9)(10).…”

Section: Discussionmentioning

confidence: 99%

“…Investigation of the molecules associated with regional lymph nodes metastasis and poor prognosis in patients with SCC would be useful in recognizing tumor behavior, accurately predicting prognosis, and increasing the ability to determine the most appropriate therapies for each patient. In recent years, S100A4, a member of the S100 calcium-binding protein family, has been associated with increased metastases; S100A4 expression correlates strongly with invasive and metastatic behavior of cultured tumor cells, including colorectal adenocarcinoma (4), bile duct adenocarcinoma (5), and human squamous cell carcinoma (6). In clinical research, elevated expression of S100A4 has been connected with metastasis and poor prognosis in breast cancer (7,8), non-small cell lung cancer (NSCLC) (9), gallbladder cancer (10), and esophageal squamous cell carcinoma (11).…”

Section: Introductionmentioning

confidence: 99%

The Evaluation of both Metastasis and Prognosis of Oral Squamous Cell Carcinoma by S100A4 and E-cadherin Immunostaining

et al. 2004

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Using immunohistochemistry, we studied the expression of S100A4 and E-cadherin in 43 oral squamous cell carcinomas (SCC) to evaluate the metastatic potential and patient survival.Expression levels of S100A4 correlated with lymph node metastasis (P=0.024) and poor prognosis (P=0.0136). Reduced E-cadherin expression was also associated with lymph node metastasis (P=0.023) and poor prognosis (P=0.0146) and was inversely correlated with S100A4 expression (P=0.011). We also found that S100A4(2+,3+)/E-cadherin(-,+) expression was significantly associated with lymph node metastasis (P=0.04) and poor prognosis (P=0.0021). Furthermore, we systematized the evaluation of oral SCC metastasis and prognosis by analyzing the expression of S100A4, E-cadherin, and other histopathological factors. Cases with total points greater than 8 were associated with lymph node metastasis (P=0.000) and poor prognosis (P=0.0022). These results indicate that S100A4, as both a single factor and in combination with E-cadherin, may be one of the most useful markers predicting the metastatic potential and prognosis of oral SCC patients.

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Induction of S100A4 gene expression inhibits in vitro invasiveness of human squamous cell carcinoma, KOSC-3 cells

Cited by 9 publications

References 22 publications

Liprin β1, a Member of the Family of LAR Transmembrane Tyrosine Phosphatase-interacting Proteins, Is a New Target for the Metastasis-associated Protein S100A4 (Mts1)

Liprin β1, a Member of the Family of LAR Transmembrane Tyrosine Phosphatase-interacting Proteins, Is a New Target for the Metastasis-associated Protein S100A4 (Mts1)

Extracellular S100A4(mts1) stimulates invasive growth of mouse endothelial cells and modulates MMP-13 matrix metalloproteinase activity

The Evaluation of both Metastasis and Prognosis of Oral Squamous Cell Carcinoma by S100A4 and E-cadherin Immunostaining

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