Effects of the regulation of polysialyltransferase ST8SiaII on the invasiveness and metastasis of small cell lung cancer cells.

Invasiveness and metastasis may seriously affect the prognosis of small cell lung cancer (SCLC). In the present study, we analyzed the effects and inherent mechanisms of action of polysialic acid-modified neural cell adhesion molecule (NCAM) on the invasive and metastatic potential of SCLC. Gene transfection and short hairpin RNA (shRNA) interference were used to enhance or inhibit, respectively, the expression of polysialyltransferase ST8SiaII in the SCLC cell line H446. We studied in vitro positive or negative changes in the invasive and metastatic potential of the SCLC cells as well as the changes in expression of genes related to signaling molecules and metastasis. When ST8SiaII expression was enhanced, the in vitro transmembrane invasion (P<0.01) and migration (P<0.01) abilities of the SCLC cells markedly increased. Phosphorylation levels of fibroblast growth factor receptor 1 (FGFR1), extracellular signal-related kinase 1/2 (ERK1/2), and matrix metalloproteinase-9 (MMP-9) in the SCLC cells were also significantly increased. In contrast, when ST8SiaII expression was inhibited, the transmembrane invasion (P<0.01) and migration (P<0.01) of the SCLC cells as well as expression of the above signaling molecules were suppressed. Polysialic acid-modified NCAM on the surface of SCLC cells is closely related to the metastatic potential of these cells; regulation of ST8SiaII may thus affect the invasiveness and metastasis of SCLC, and these processes may be associated with phosphorylation of FGFR1, ERK1/2 or MMP-9.