An association between high Ly-6A/E expression on tumor cells and a highly malignant phenotype.
Murine Ly-6 is a molecule expressed by various cells, including several types of hematopoietic cells such as pluripotent stem cells, and activated T cells. Ly-6 is also expressed on tumor cells originating from a variety of tissues. Preliminary observations suggested that the expression of Ly-6A/E is up-regulated on highly tumorigenic variants of polyoma-virus(PyV)-transformed BALB/c 3T3 cells as compared with weakly tumorigenic variants. On the basis of these observations, we sorted PyV-transformed A3C cells or DA3 mammary adenocarcinoma cells into stable sub-populations expressing high or low levels of membrane or mRNA Ly-6A/E. In vivo studies indicated that the high-Ly-6A/E-expressing cells in both tumor systems expressed a considerably more malignant phenotype (higher efficiency in local tumor production as well as in lung colonization) than low-Ly-6A/E expressors. Since the high-Ly-6A/E expressors did not exhibit any growth advantage in vitro over low Ly-6A/E expressors, we concluded that interactions of the former cells with micro-environmental factors operating in vivo (e.g., Ly-6A/E ligands) conferred upon these cells a highly malignant phenotype. Apart from the difference in Ly-6A/E expression, no other phenotypic characteristics distinguished highly from weakly malignant tumor cells. Similarly to T cells, where antibodies to Ly-6 transduce (or co-transduce) a proliferative signal, antibodies to Ly-6A/E were found to transduce a mitogenic signal to high-Ly-6A/E-expressing tumor cells but not to low-Ly-6A/E expressors. Taken together, these results show that Ly-6A/E expression is directly or indirectly associated in vivo with a highly malignant phenotype of 2 types of non-lymphoid murine tumors.
Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel.
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BZ
Katz
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Eshel
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Sagi-Assif
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IP
Witz
D016475:3T3 Cells; D000818:Animals; D000950:Antigens, Ly / Q000032:analysis* / Q000235:genetics; D001483:Base Sequence; D002461:Cell Line, Transformed; D015870:Gene Expression; D008175:Lung Neoplasms / Q000209:etiology / Q000473:pathology; D008325:Mammary Neoplasms, Experimental; D008565:Membrane Proteins / Q000032:analysis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000737:chemistry*; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D014407:Tumor Cells, Cultured
D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D012333:RNA, Messenger