Copy the page URI to the clipboard
Hulgaard, Egil Fabritius
(1998).
DOI: https://doi.org/10.21954/ou.ro.00010203
Abstract
Metastasis is a complex multistep process allowing otherwise localised tumour cells to migrate to other organs. To elucidate this mechanism further we compared the mRNA level of non-metastatic CSML-0 to metastatic CSML-100 and VMR-Li using differential display. This approach led to the identification of ten different genes differentially expressed between two closely related CSML cell lines. Cloning, sequencing and database analysis suggested the cloned fragments to be related to six genes with known coding sequence. MMTV, Collagen XI α1 and PACE4 were found in CSML-0, while Cystatin C, Lamin C and Ly-6A/E were upregulated in CSML-100. Also four fragments, NN18 found in CSML-0 and NN9, NN30 and NN32 found in CSML-100, not related to any known gene were cloned. When tested against a panel of mouse tumour cell lines, a pattern of expression for Collagen XI α1, PACE4, Cystatin C, Lamin C, Ly-6A/E, NN9 and NN30 connecting these genes to the metastatic process were found. Cystatin C protein staining of cell lines and CSML tumour tissue further suggested an involvement of this proteinase inhibitor in tumour progression. This is the first report connecting PACE4 and Collagen XI α1 to tumour progression and points to new proteins potentially.utilised by colonising cells. The NN30 gene fragment was selected for further identification and characterisation. The full-length clone revealed a 338 amino acid 39 kDa protein, lacking obvious homologues in the EMBL database. We temporarily named this protein E30. In situ hybridisation and immunostainings demonstrated that this protein was highly expressed in epithelial cells, in testis and in ovary, in embryonic tissue as well as in extra embryonic. This gene is part of a previously undescribed gene family as indicated by human and C. elegans ESTs homologous to E30. Transfection of E30 into non-metastatic CSML-0 cells rendered these cells metastatic in 2 out of 3 mice in an experimental metastasis assay. Metastatic nodules were not only confined to the lung, but both mice produced liver metastasis. I therefore report the cloning of a gene expressed in epithelial cells and capable of inducing metastasis to the liver and lung.
CORE (COnnecting REpositories)
CORE (COnnecting REpositories)
