Retroviral-mediated transmission of a mouse VL30 RNA to human melanoma cells promotes metastasis in an immunodeficient mouse model.
Infection of a human melanoma cell line by a retroviral vector resulted in transmission of a mouse VL30 (mVL30-1) retroelement RNA to some of the cells infected by the retrovirus, followed by synthesis, integration, and expression of the mVL30-1 cDNA. One vector carried a tissue factor (TF) transgene that generated high TF melanoma clones, and another vector was a control without the TF transgene that generated low TF clones. Some high TF melanoma clones contained the mVL30-1 retroelement and others did not, and some low TF melanoma clones contained the mVL30-1 retroelement and others did not. Each type of melanoma clone was tested for its metastatic potential in severe combined immunodeficient (SCID) mice, by i.v. injection of the cells to generate lung tumors. None of the low TF clones that either contained or lacked the mVL30-1 retroelement generated lung tumors, consistent with earlier results showing that high TF expression promoted metastasis. The high TF clones containing the mVL30-1 retroelement were strongly metastatic, in contrast to the high TF clones lacking the mVL30-1 retroelement, which were weakly metastatic. Southern hybridization analyses showed that the mVL30-1 cDNA integrated into different genomic sites in different melanoma clones, suggesting that the effect of the mVL30-1 retroelement on metastasis depends not on integration per se but instead on expression of the mVL30-1 RNA. A role for the mVL30-1 RNA in metastasis and possibly other cell functions is an unexpected finding, because the RNA appears to lack significant coding potential for a functional protein. The metastatic effect might be mediated directly by a noncoding mVL30-1 RNA or by a peptide or small protein encoded by one of the short ORFs in the mVL30-1 RNA.
Song
Xu
X
Department of Molecular Biophysics and Biochemistry and Internal Medicine, Yale University, New Haven, CT 06520, USA.
Wang
Baiyang
B
Bromberg
Michael
M
Hu
Zhiwei
Z
Konigsberg
William
W
Garen
Alan
A
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D018076:DNA, Complementary / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000378:metabolism* / Q000821:virology; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D016133:Polymerase Chain Reaction; D012313:RNA / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013925:Thromboplastin / Q000235:genetics; D014162:Transfection; D019076:Transgenes; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D012313:RNA; D013925:Thromboplastin