Differentiation of a Cell Line of Human Cervical Argyrophil Small Cell Carcinoma to Macrophage Lineage Cells

To investigate the origin of argyrophil small cell carcinoma (ASCC) of the uterine cervix, we examined the influence of dibutyryl cyclic adenosine 3′,5′‐monophosphate (dB‐cAMP), a known differentiation inducer, on the characteristics of an ASCC cell line, TC‐YIK, which has been shown to be a useful in vitro experimental model of ASCC. In TC‐YIK cells after treatment with dB‐cAMP, two specific antigenic markers of macrophages, CD14 and human leukocyte antigen‐DR, were detected by flow cytometric analysis. In addition, interferon‐γ mRNA was detected by reverse transcription‐polymerase chain reaction and interferon‐γ protein was detected by ELISA. More than 90% of the cells stained positive for α‐naphthyl butyrate esterase, 1% of the cells showed phagocytotic activity against Micrococcus lysodeikticus, and 22% of the cells had M. lysodeikticus adsorbed on their surface. Furthermore, granulocyte‐macrophage colony stimulating factor accelerated the proliferation of TC‐YIK cells. These results indicate that dB‐cAMP promotes differentiation of ASCC cells to macrophages. In contrast, less than 10% of the cells showed stellate morphology, suggesting differentiation to neuronal cells after treatment with dB‐cAMP, as reported previously. Thus, TC‐YIK cells have been shown to differentiate both into macrophage lineage cells and neuronal cells, suggesting that ASCC originates from undifferentiated stem cells.