DIFFERENTIAL EXPRESSION AND RESPONSE OF GROWTH FACTORS IN DIFFERENT METASTATIC VARIANTS OF HUMANPULMONARY GIANT CELL CARCINOMA

The cell lines PGbE1 and PGLH7, which have high and low metastatic potential respectively, were two different variants isolated from human pulmonary giant cell carcinoma cell line PG. This study compared the expression and response of several growth factors TGFa, TGFb, bFGF, IL 6, IL 8 and ANG in the two cell lines. By using RT PCR analysis and thymidine incor poration assay, it was found that IL 6, TGFa and their receptors IL 6R and EGFR were expressed at higher level in PGbE1 cells than in PGLH7 cells, while no significant differences were found in the expression of ANG, bFGF, IL 8, IL 8R and TGFβ. Recombinant IL 6 and TGFα stimulated the proliferation of both cells, while TGFβ had dual effects. These results suggest that ANG, bFGF IL 6, IL 8 and TGFα, β may be involved in the proliferation of pulmonary giant cell carcinoma via autocrine mechanism, and IL 6 and TGFa may play an important role in the metastasis of tumor cells.

The cellular and molecular mechanism of laminin glycopeptides on anti -metastasis

To further study the anti metastasis mechanism of laminin glycopeptides on carcinoma cell proliferation, apoptosis and the secretion of matrix metalloproteinases Methods Human hepatocellular carcinoma cells in serum free medium were incubated on laminin coated substrate with or without laminin glycopeptides at a final concentration of 50?μg/ml The total number of surviving cells after incubating for the indicated time was assayed by MTT assay DNA synthesis of the incubated cells was detected by 3H TdR incorporation Cell cycle was analysed by FACS The mitotic index of Giemsa stained cells was assessed Cell apoptosis was detected by both FACS and an acridine orange staining method Matrix metalloproteinase secretion was analysed by gelatin zymography Results The total number of surviving cells incubated on laminin in the absence of laminin glycopeptides was significantly larger than that in the presence of laminin glycopeptides Laminin promoted 3H TdR incorporation of carcinoma cells, decreased the percentage of cells in G1 phase and increased the percentage of cells in S phase In contrast, laminin glycopeptides could inhibit the effect of laminin as shown by 3H TdR incorporation and cell cycle analysis The percentage of cells in G2+M phase and the mitotic index among various groups showed no significant difference Matrix metalloproteinases secretion from cells treated by laminin glycopeptides was much less compared to that without the treatment by laminin glycopeptides Conclusion Laminin may stimulate cell proliferation, while laminin glycopeptides could significantly inhibit the effect of laminin by inhibiting DNA synthesis and arresting the carcinoma cell cycle from G1 to S phase These effects may inhibit not only tumor growth of the primary carcinoma, but also the establishment of metastases at ectopic tissues Laminin glycopeptides could also inhibit the secretion of matrix metalloproteinases from carcinoma cells and this may contribute to their decreased invasive and metastatic phenotype This study further revealed the cellular and molecular mechanism of laminin glycopeptides on anti metastasis