Furthermore, S100A4 levels were determined because recent reports have suggested a possible association between MMPs, TIMPs, and the metastasis-associated gene S100A4.
Tumor suppressor gene MTS1/p16 (cyclin-dependent kinase-4 inhibitor) and a putative tumor metastasis suppressor gene nm23 (nucleoside diphosphate A kinase) have been identified in a variety of human tumors but have not been well studied in mesenchymal neoplasms.
The results suggest that S100A4 might induce metastasis by influencing the function of p53 as well as through its interaction with myosin and that any mechanism is independent of the mutational status of p53.
High levels of S100A4 were found to significantly correlate with histological grade (P=0.030) and loss of oestrogen receptor (P=0.046), but not to the time interval between surgery and development of distant metastasis (P=0.51) or to patient survival (P=0.89).
Mutations of the cell cycle arrest gene p21WAF1, but not the metastasis-inducing gene S100A4, are frequent in oral squamous cell carcinomas from Sudanese toombak dippers and non-snuff-dippers from the Sudan, Scandinavia, USA and UK.
Using the National Center for Biotechnology Information Serial Analysis of Gene Expression database, we found that S100A4, a calcium-binding protein previously implicated in metastasis, was expressed in five of seven pancreatic carcinoma libraries but not in the two normal pancreatic duct libraries.
Taken together with the results from our parallel studies of human bladder cancer, these data suggest a significant role for S100A4 in bladder cancer metastasis and identify a potential new target for systemic therapy in patients with this disease.
The percentage of specimens stained for S100A4 in the epithelial cells is significantly higher for those isolated from carcinomas and metastases than from the corresponding normal tissue, and from metastases than from corresponding carcinoma (Fisher Exact text, P<0.0016, P=0.04, respectively).
To investigate whether S100A4 plays an important role in the invasion and metastasis of gastric cancers, we examined the gene mutations in the coding regions and expression patterns of the S100A4 in gastric adenocarcinoma in Korea.
Using a panel of genes identified by suppression subtractive hybridization of cDNAs from individual primary tumours and a metastasis, some cDNAs were found to exhibit a differential pattern of expression associated with the expression of S100A4 protein (including osteopontin, S100A9, claudin 2 and several Expressed Sequence Tags sequences).
Consideration of clinical studies in conjunction with evidence from experimental animal models reveals that the tyrosine kinase receptor erbB1/EGFR, the calcium binding protein S100A4 and the the cell cycle arrest/apoptosis-inducing p53 protein are amongst the most promising targets for therapy against metastatic disease in patients with bladder cancer.
These data suggest that S100A4 localizes to the leading edge in a calcium-independent manner, and identification of the proteins that are involved in localizing S100A4 to the lamellipodial structures may provide novel insight into the mechanism by which S100A4 regulates metastasis.
Mutations of the cell cycle regulatory genes p16INK4A and p21WAF1 and the metastasis-inducing gene S100A4 are infrequent and unrelated to p53 tumour suppressor gene status and data on survival in oropharyngeal squamous cell carcinomas.
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.
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.
S100A4 expression with reduced E-cadherin expression predicts distant metastasis of human malignant melanoma cell lines in the NOD/SCID/gammaCnull (NOG) mouse model.