S100 calcium binding protein A4 (S100A4) and cysteine-rich angiogenic inducer 61 (CYR61) play important roles in epithelial-mesenchymal-transition (EMT), invasion and metastasis by promoting cancer cell motility.
We found the mRNA and protein levels of S100A4 expression in ESCCs was significantly upregulated, and more importantly, that expression of S100A4 and E cadherin are strongly negatively correlated in patients who had metastasis.
These findings suggest that S100A4 protects gastric cancer cells from anoikis by regulation of αv and α5 integrin expression, which sheds a novel light for the role of S100A4 in cancer metastasis.
Focusing on S100A4, S100A8 and S100A9, in this review we discuss the role these proteins play in primary tumors and in the development of metastases, in particular during the formation of pre-metastatic niches.
Immune-histochemical analysis of 239 patient tissue samples revealed a correlation of higher CYR61 and S100A4 expression with invasive breast cancer and metastasis.
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 protein belongs to the S100 subfamily, which has grown to be one of the large subfamilies of the EF-hand Ca(2+)-binding proteins, and overexpression of S100A4 is suggested to associate with cell proliferation, invasion, and metastasis.
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).
S100A4 is a well established marker and mediator of metastatic disease, but the exact mechanisms responsible for the metastasis promoting effects are less well defined.
Given the associations of S100A4, nuclear factor-kB (NF-kB/RelA) and MMP-9 with metastasis in a variety of malignancies, we explored a potential role of S100A4 in HCC metastasis and its mechanism.
Metastasis-associated in colon cancer 1 (MACC1) and S100 calcium-binding protein A4 (S100A4) are prominent inducers of tumor progression and metastasis.
Overall, our results suggest the existence of evolutionarily conserved pathways used by S100A4 to promote metastatic dissemination, with potential prognostic and therapeutic implications for metastasis by cancers that preferentially exploit nerve tract migration routes.
However, it is not known how many of these interactions are required for S100A4-promoted metastasis, thus hampering the design of specific inhibitors of S100A4-induced metastasis.
All the data in the present study suggested that S100A4 might contribute to HCC invasion and metastasis through two paths of matrix metalloproteinase (MMP9) secretion regulation and strengthened motility and invasion properties.
In transfected cells, a suppression of the capacity to give skeletal metastases upon intracardial injection into nude rats was observed in cell clones with reduced expression of CAPL mRNA and protein, whereas in vitro and in vivo cell proliferation and tumorigenicity were unchanged.