• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.613-615
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• 2012

The aim of this study was to ana1yze T-cell lymphoma invasion and metastasis-inducing factor 1 (Tiam1) expression in 1ung cancer patients. A total of 204 patients with lung cancer tissue lesions were enrolled in the present study, along with 40 cases of normal lung tissue and 40 of normal fetal lung tissue. Tiam1 protein expression level was determined using intensity quantitative analysis, for comparison in lung cancer, metastatic, normal lung, and fetal lung tissue. The positive unit (PU) of Tiam1 was $13.5{\pm}5.42$ in lung cancer,$5.67{\pm}1.56$ in norma1 epithelial cells, and $5.89{\pm}1.45$ in fetal lung epithelial cells. The value in the lung cancer tissue was significantly higher than that in the normal lung tissue and the fetal lung tissue (P<0.01). The Tiam1 PU values with lymph node metastasis and without 1ymph node metastasis were $15.2{\pm}4.34$ and $12.5{\pm}4.23$, respectively, and the difference was statistically significant (P<0.05). The Tiam1 PU values in different tumor, nodes, metastasis (TNM) stages, III-IV period, and I-II phase were $14.7{\pm}4.14$ and $11.0{\pm}5.34$ (P<0.05). A correlation was found between Tiam1 expression and the age of patient, tumor size, tumor type, and tumor differentiation. Tiam1 protein expression in the lung tumor tissue is significantly higher than that in the normal lung tissue and fetal lung tissue. Tiam1 expression may be closely related to lung cancer development and metastasis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.201-208
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• 2013

Objective: To investigate changes in the invasive capacity of gastric cancer cells in vitro after expression inhibition of T lymphoma invasion and metastasis inducing factor 1 (Tiam 1) and underlying mechanisms. Methods: Using adhesion selection, two subpopulations with high ($M_H$) or low ($M_L$) invasive capacity were separated from the human gastric cancer cell line MKN-45 ($M_0$). Tiam 1 antisense oligodeoxynucleotide (ASODN) was transfected into $M_H$ cells with liposomes, and expression of Tiam 1 mRNA and protein was determined by RT-PCR and quantitative cellular-ELISA. Changes in the cytoskeleton, invasive capacity in vitro and expression of ras-related $C_3$ botulinum toxin substrate 1 (Rac 1), integrin ${\beta}1$ and matrix metalloproteinase 2 (MMP 2) between Tiam 1 ASODN transfected $M_H$ cells and non-transfected cells were observed by HE staining, cytoskeletal protein staining, scanning electron microscopy, Boyden chamber tests and cyto-immunohistochemistry. Results: A positive correlation existed between the expression level of Tiam l mRNA or protein and the invasion capacity of gastric cancer cells. After ASODN treatment ($0.43{\mu}M$ for 48 h), Tiam 1 mRNA transcription and protein expression in $M_H$ cells were decreased by 80% and 24% respectively (P < 0.05), compared with untreated controls, while invasive capacity in vitro was suppressed by 60% (P < 0.05). Morphologic and ultrastructural observation also showed that ASODN-treated $M_H$ cells exhibited smooth surfaces with obviously reduced filopodia and microspikes, which resembled $M_0$ and $M_L$ cells. Additionally, cytoskeletal distribution dramatically altered from disorder to regularity with reduced long filament-like structure, projections, pseudopodia on cell surface, and with decreased acitn-bodies in cytoplasm. After Tiam 1 ASODN treatment, the expression of Rac 1 and Integrin ${\beta}1$ in $M_H$ cells was not affected (P > 0.05), but that of MMP 2 in $M_H$ cells was significantly inhibited compared with untreated cells (P < 0.05). Conclusion: Over-expression of Tiam-1 contributes to the invasive phenotype of gastric cancer cells. Inhibition of Tiam 1 expression could impair the invasive capacity of gastric cancer cells through modulating reconstruction of the cytoskeleton and regulating expression of MMP 2.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6305-6309
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• 2013

Background: TIAM2, a Rac guanine nucleotide exchange factor, is closely associated with cell adherence and migration. Here, we aimed to investigate the role of TIAM2 in non-small cell lung cancer (NSCLC) cells. Materials and Methods: A small interference RNA (siRNA) was introduced to silence the expression of TIAM2. Invasion and motility assays were then performed to assess the invasion and motility potential of NSCLC cells. GST-pull down assays were used to detect activation of Rac1. Results: TIAM2 was highly expressed in NSCLC cells. Knockdown of TIAM2 inhibited the invasion and motility, and suppressed activation of Rac1. Further experiments demonstrated that knockdown of TIAM2 could up-regulate the expression of E-cadherin, and down-regulate the expression of MMP-3, Twist and Snail. Conclusions: Our data suggest that TIAM2 can promote invasion and motility of NSCLC cells. Activation of Rac1 and regulation of some EMT/invasion-related genes may be involved in the underlying processes.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3681-3684
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• 2013

Deregulated miRNAs participate in osteosarcoma genesis. In this study, the expression of miRNA-218 in human osteosarcomas, adjacent normal tissues and Saos-2 human osteosarcoma cells was first assessed. Then the precise role of miRNA-218 in osteosarcoma cells was investigated. Upon transfection with a miR-218 expression vector, the proliferation of Saos-2 human osteosarcoma cells determined using the ATPlite assay was significantly suppressed, whilw migration of Saos-2 cells detected by wound healing and invasion determined using transwells were dramatically inhibited. Potential target genes of miR-218 were predicted and T-cell lymphoma invasion and metastasis 1 (TIAM1) and matrix metalloproteinase 2 (MMP2) and 9 (MMP9) were identified. This was confirmed by western blotting, which showed that miR-218 expression inhibited TIAM1, MMP2 and MMP9 protein expression. Collectively, these data suggest that miR-218 acts as a tumor suppressor in osteosarcomas by down-regulating TIAM1, MMP2 and MMP9 expression.

• Journal of Chest Surgery
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• v.42 no.2
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• pp.141-147
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• 2009

Background: We performed this study to identify the tumor suppressor genes located in the long arm of chromosome 21 in non-small cell lung cancer. Material and Method: The genes of USP25 in 21q11.2, NCAM2, ADAMTS1 in 21q21.2, and Claudin-8 (CLDN8), Claudin-17 (CLDN17) and TIAM1 in 21q22.1 were investigated for their gene expressions, genetic alterations and promoter methylation. Result: The expressions of CLDN8 and CLDN17 were significantly decreased in 7 (L132, H157, H358, H522, H1299, H1703 and HCC2108) of 13 cell lines, and the expression of ADAMTS1 was also significantly reduced in 6 cell lines (A549, SW900, H1299, H1373, H1703 and H1793). There were no genetic alterations by PCR-SSCP and cDNA cloning in the cell lines with a decreased gene. In the cell lines with a decreased gene expression, the mRNA expression was increased significantly with treatment of 5-Aza-CdR. Conclusion: These results suggest that the ADMTS1, CLDN8 and CLDN17 may act as tumor suppressor genes.