Isolation and characterization of a gene specifically expressed in different metastatic cells and whose deduced gene product has a high degree of homology to a Ca2+-binding protein family.

Abstract

The gene mtsl, which is expressed specifically in metastatic cells, was isolated by molecular cloning coupled with differential DNA reassociation. Transcription of mtsl was found not only in tumor cells, but also in normal cells; homologous RNA was detected only in spleen, thymus, bone marrow, and blood lymphocytes. DNA sequencing of mtsl revealed an open reading frame containing information for a peptide of 101 amino acids, and the amino acid sequence suggested that the mtsl protein was identical to the previously isolated Ca2+-binding mouse protein (Jackson-Grusby et al. 1987; Goto et al. 1988). Thus, the mtsl protein is a member of the calcium-modulated protein family, and our data indicate that mtsl is involved in regulating the metastatic behavior of tumor cells.

Expression of antisense RNA to S100A4 gene encoding an S100-related calcium-binding protein suppresses metastatic potential of high-metastatic Lewis lung carcinoma cells

“…Enforced expression of the S100A4 protein in tumor cells results in enhancement of motility (Takenaga et al, 1994a;Ford and Zain, 1995). S100A4 is also expressed in normal cells and tissues which exhibit highly motile ability (JacksonGrusby et al, 1987;Ebralidze et al, 1989;Ford and Zain, 1995;Grigorian et al, 1993;Takenaga et al, 1994b). Furthermore, the expression of S100A4 was induced during the di erentiation of promyelocytic leukemia HL60 cells, coinciding with the expression of motile phenotype (Takenaga et al, 1994c).…”

“…These results strongly implicate S100A4 in cytoskeletal dynamics and/or cell motility. Supporting this, embryonic trophoblast cells, lymphoid cells and macrophages, all of which are highly motile, are found to express a relatively high amount of S100A4 (Jackson-Grusby et al, 1987;Ford and Zain, 1995;Ebralidze et al, 1989;Grigorian et al, 1993;Takenaga et al, 1994b,c). Furthermore, we and others have recently demonstrated the enhanced cell motility in S100A4 cDNA-transfected tumor cells (Takenaga et al, 1994a;Ford et al, 1995).…”

“…In addition, recent studies have suggested the involvement of the gene product in the regulation of metastasis. S100A4 has been reported to be speci®cally expressed in metastatic tumor cells (Ebralidze et al, 1989), and be able to induce metastatic phenotype in a benign rat mammary epithelial cell line (Davies et al, 1993) and in B16 melanoma cells (Parker et al, 1994).…”

Human S100A4 (p9Ka) induces the metastatic phenotype upon benign tumour cells

“…Although some proteins associated with the process of metastasis have been identi®ed, there is little information on proteins and their genes which can cause metastasis in human cancers. In rodent systems, such a gene and its protein product have been identi®ed, namely S100A4, also known previously as p9Ka, mts1, pEL98, 18A2, 42A (Barraclough et al, 1987b;Ebralidze et al, 1989;Goto et al, 1988;Jackson-Grusby et al, 1987;Masiakowski and Shooter, 1988). In cultured mammary cells of mouse (Ebralidze et al, 1989) and rat (Dunnington, 1984), the level of S100A4 or its mRNA correlates with the metastatic potential of the cells.…”

“…In rodent systems, such a gene and its protein product have been identi®ed, namely S100A4, also known previously as p9Ka, mts1, pEL98, 18A2, 42A (Barraclough et al, 1987b;Ebralidze et al, 1989;Goto et al, 1988;Jackson-Grusby et al, 1987;Masiakowski and Shooter, 1988). In cultured mammary cells of mouse (Ebralidze et al, 1989) and rat (Dunnington, 1984), the level of S100A4 or its mRNA correlates with the metastatic potential of the cells. Furthermore, transfection of the rat S100A4 gene into diploid benign rat mammary epithelial cells and expression of S100A4, confers on the cells stable metastatic capability , suggesting that elevated expression of S100A4 can cause metastasis in a benign, tumorigenic, but non-metastatic cell line.…”