Expression of a novel factor in human breast cancer cells with metastatic potential

Clinical and experimental evidence suggests that tumor cells shed into the circulation from solid cancers are ineffective in forming distant metastasi s unless the cells are able to respond to growth conditions offered by the secondary organs. To identify the phenotypic properties that are specific f or such growth response, we injected carcinoma cells, which had been recove red from bone marrow micrometastases in a breast cancer patient who was cli nically devoid of overt metastatic disease and established in culture, into the systemic circulation of immunodeficient rats. The animals developed me tastases in the central nervous system, and metastatic tumor cells were iso lated with immunomagnetic beads coated with an antibody that was reactive w ith human cells. The segregated cell population was compared with the injec ted cells by means of differential display analysis, and two candidate frag ments were identified as upregulated in the fully metastatic cells, The fir st was an intracellular effector molecule involved in tyrosine kinase signa ling, known to mediate nerve growth factor-dependent promotion of cell surv ival. The second was a novel gene product (termed candidate of metastasis-1 ), presumably encoding a DNA-binding protein of helix-turn-helix type. Cons titutive expression of candidate of metastasis-1 seemed to distinguish brea st cancer cells with metastatic potential from cells without metastatic pot ential. Hence, our experimental approach identified factors that may mediat e the growth response of tumor cells upon establishment in a secondary orga n and, thereby, contribute to the metastatic phenotype.