Abstract
Madin-Darby canine kidney (MDCK) epithelial cells form branching tubules in three-dimensional collagen gel in the presence of hepatocyte growth factor (HGF). Membrane type-1 matrix metalloproteinase (MT1-MMP), expression of which was induced by collagen-gel culture, was demonstrated to play an essential role in tubular formation (Y. Kadono et al. Biochem Biophys Res Commun 1998; 251: 681–7 [13]). Oncogenic transformation of MDCK cells by erbB2 and v-src induced expression of MT1-MMP, loss of cell-cell adhesion and scattered invasion into collagen gel. mRNA differential display and Northern hybridization identified metastasis-associated mts1 as one of the genes co-induced with MT1-MMP by oncogenic transformation or collagen-gel culture of MDCK cells. Expression of antisense RNA to mts1 in MDCK cells interfered with the extension of tubules into the collagen gel, however, it did not affect the morphological changes induced by HGF in culture on plastic dishes. ErbB2-transformant transfected with mts1 antisense construct, which showed unaltered morphology in culture on plastic dishes, did not scatter into collagen gel but formed aggregates. These results suggested that Mts1 contributes not only to tumor invasion but also to kidney tubulogenesis in cooperation with MT1-MMP. The coordinated action of MT1-MMP and Mts1, which is responsible for the highly invasive properties of mesenchymal cells, may be involved in epithelial tubulogenesis and invasion of malignant carcinoma cells.
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References
Sato H, Takino T, Okada Y et al. A matrix metalloproteinase expressed on the surface of invasive tumour. Nature 1994; 370: 61–5.
Kinoh H, Sato H, Tsunezuka Y et al. MT-MMP, the cell surface activator of proMMP-2 (pro-gelatinase A), is expressed with its substrate in mouse tissue during embryogenesis. J Cell Sci 1996; 109: 953–9.
Nakahara H, Howard L, Thompson EW et al. Transmembrane/cytoplasmic domain-mediated membrane type 1-matrix metalloprotease docking to invadopodia is required for cell invasion. Proc Natl Acad Sci USA 1997; 94: 7959–64.
Ohuchi E, Imai K, Fujii Y et al. Membrane type 1 matrix metalloproteinase digests interstitial collagens and other extracellular matrix macromolecules. J Biol Chem 1997; 272: 2446–51.
d’Ortho MP, Will H, Atkinson S et al. Membrane-type matrix metalloproteinases 1 and 2 exhibit broad-spectrum proteolytic capacities comparable to many matrix metalloproteinases. Eur J Biochem 1997; 250: 751–7.
Nomura H, Sato H, Seiki M et al. Expression of membrane-type matrix metalloproteinase in human gastric carcinomas. Cancer Res 1995; 55: 3263–6.
Yoshizaki T, Sato H, Maruyama Y et al. Increased expression of membrane type 1-matrix metalloproteinase in head and neck carcinoma. Cancer 1997; 79: 139–44.
Tokuraku M, Sato H, Murakami S et al. Activation of the precursor of gelatinase A/72 kDa type IV collagenase/MMP-2 in lung carcinomas correlates with the expression of membrane-type matrix metalloproteinase (MT-MMP) and with lymph node metastasis. Int J Cancer 1995; 64: 355–9.
Ueno H, Nakamura H, Inoue M et al. Expression and tissue localization of membrane-type 1, 2, and 3 matrix metalloproteinases in human invasive breast carcinoma. Cancer Res 1997; 57: 2055–60.
Okada A, Bellocq JP, Rouyer N et al. Membrane-type matrix metalloproteinase (MT-MMP) gene is expressed in stromal cells of human colon, breast, and head and neck carcinomas. Proc Natl Acad Sci USA 1995; 92: 2730–4.
Tsunezuka Y, Kinoh H, Takino T et al. Expression of membrane-type matrix metalloproteinase 1 (MT1-MMP) in tumor cells enhances pulmonary metastasis in an experimental metastasis assay. Cancer Res 1996; 56: 5678–83.
Kadono Y, Okada Y, Namiki M et al. Transformation of epithelial Madin-Darby canine kidney cells with p60(v-src) induces expression of membrane-type 1 matrix metalloproteinase and invasiveness. Cancer Res 1998; 58: 2240–4.
Kadono Y, Shibahara K, Namiki M et al. Membrane type 1-matrix metalloproteinase is involved in the formation of hepatocyte growth factor/scatter factor-induced branching tubules in madin-darby canine kidney epithelial cells. Biochem Biophys Res Commun 1998; 251: 681–7.
Sherbet GV, Lakshmi MS. S100A4 (MTS1) calcium binding protein in cancer growth, invasion and metastasis. Anticancer Res 1998; 18: 2415–21.
Lloyd BH, Platt HA, Rudland PS et al. Human S100A4 (p9Ka) induces the metastatic phenotype upon benign tumour cells. Oncogene 1998; 17: 465–3.
Noritake H, Miyamori H, Goto C et al. Overexpression of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in metastatic MDCK cells transformed by v-src. Clin Exp Metastasis 1999; 17: 105–10.
Liotta L A. Cancer cell invasion and metastasis. Sci Am 1992; 266: 54–9.
Barraclough R, Savin J, Dube SK, Rudland PS. Molecular cloning and sequence of the gene for p9Ka. A cultured myoepithelial cell protein with strong homology to S-100, a calcium-binding protein. J Mol Biol 1987; 198: 13–20.
Ebralidze A, Tulchinsky E, Grigorian M et al. 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. Genes Devel 1989; 3: 1086–93.
Lukanidin EM, Georgiev GP. Metastasis-related mts1 gene. Curr Top Microbiol Immunol 1996; 172-95.
Takenaga K, Nakamura Y, Sakiyama S. Expression of antisense RNA to S100A4 gene encoding an S100-related calcium-binding protein suppresses metastatic potential of high-metastatic Lewis lung carcinoma cells. Oncogene 1997; 14: 331–7.
Gibbs FE, Wilkinson MC, Rudland PS, Barraclough R. Interactions in vitro of p9Ka, the rat S-100-related, metastasis-inducing, calcium-binding protein. J Biol Chem 1994; 269: 18992–9.
Takenaga K, Nakamura Y, Endo H, Sakiyama S. Involvement of S100-related calcium-binding protein pEL98 (or mts1) in cell motility and tumor cell invasion. Jpn J Cancer Res 1994; 85: 831–9.
Watanabe Y, Usuda N, Tsugane S et al. Calvasculin, an encoded protein from mRNA termed pEL-98, 18A2, 42A, or p9Ka, is secreted by smooth muscle cells in culture and exhibits Ca(2+)-dependent binding to 36-kDa microfibril-associated glycoprotein. J Biol Chem 1992; 267: 17136–40.
Watanabe Y, Usada N, Minami H. et al. Calvasculin, as a factor affecting the microfilament assemblies in rat fibroblasts transfected by src gene. FEBS Lett 1993; 324: 51–5.
Lakshmi MS, Parker C, Sherbet GV. Metastasis associated MTS1 and NM23 genes affect tubulin polymerisation in B16 melanomas: a possible mechanism of their regulation of metastatic behaviour of tumours. Anticancer Res 1993; 13: 299–303.
Merzak A, Parker C, Koochekpour S et al. Overexpression of the 18A2/mts1 gene and down-regulation of the TIMP-2 gene in invasive human glioma cell lines in vitro. Neuropathol Appl Neurobiol 1994; 20: 614–9.
Bjornland K, Winberg JO, Odegaard OT et al. S100A4 involvement in metastasis: deregulation of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in osteosarcoma cells transfected with an anti-S100A4 ribozyme. Cancer Res 1999; 15: 4702–8.
Klingelhofer J, Ambartsumian NS, Lukanidin EM. Expression of the metastasis-associated mts1 gene during mouse development. Dev Dyn 1997; 210: 87–95.
Pulyaeva H, Bueno, J Polette M et al. MT1-MMP correlates with MMP-2 activation potential seen after epithelial to mesenchymal transition in human breast carcinoma cells. Clin Exp Metastasis 1997; 15: 111–20.
Gilles C, Polette M, Birembaut P et al. Expression of c-ets-1 mRNA is associated with an invasive, EMT-derived phenotype in breast carcinoma cell lines. Clin Exp Metastasis 1997; 15: 519–26.
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Miyamori, H., Hasegawa, K., Kim, KR. et al. Expression of metastasis-associated mts1 gene is co-induced with membrane type-1 matrix metalloproteinase (MT1-MMP) during oncogenic transformation and tubular formation of Madin Darby canine kidney (MDCK) epithelial cells. Clin Exp Metastasis 18, 51–56 (2000). https://doi.org/10.1023/A:1026523418456
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DOI: https://doi.org/10.1023/A:1026523418456