Cell‐cycle‐dependent invasion in vitro by rat ascites hepatoma cells

Abstract

The relationship between cell cycle and experimental metastasis of tumor cells in vivo has been investigated, but it remains to be elucidate which step of metastasis, or whether tumor-cell invasion in particular, depends on cell cycle. We previously reported an in vitro cell-monolayer invasion (transcellular migration) assay system, in which the invasive capacity of tumor cells is measured by counting tumor cells penetrating beneath a cultured mesothelial cell monolayer after tumor-cell seeding. Using our invasion assay system, the relationship between invasive capacity and cell-cycle distribution of MMI cells, a highly invasive clone of rat ascites hepatoma AHI30, was investigated. Invasive capacity of aphidicolin- or hydroxyurea-synchronized tumor cells enriched in G1/S-early S-phase cells was about 2 to 6 times higher than that of asynchronous cells. According to time-course experiments to examine the relationship between invasive capacity and the size of fraction of cells in each phase after release from an aphidicolin or a nocodazole block, it was suggested that MMI cells are most invasive in G1/S-S phase. Phagokinetic assay using colloidal gold particles showed that one possible reason for the enhanced invasiveness might be the increased cell motility in such phases, as suggested by the in vitro invasion assay.

Screening of five specific cell cycle inhibitors using a T Cell lymphoma cell line synchrony/release assay

“…Indeed, many studies have reported conflicting results. Pande et al (1996) showed that hydroxyurea leads to Gl/S block with the majority of cells of a rat fibroblast cell line in G1 phase while Iwasaki et al (1995) obtained an S phase block using rat hepatoma cells. We obtained early S synchronized cells using CEM cells, a T cell lymphoma cell line with a fast cell cycle.…”

Adenovirus-mediated p16/CDKN2 gene transfer suppresses glioma invasion in vitro

“…These data are consistent with a previous study showing that transfer of the Rb cDNA to cancer cells decrease their invasiveness in a cell-cycle independent way (Li et al, 1996). In addition, the invasive capacity of aphidicolin-or hydroxiurea-synchronized hepatoma cells enriched in G 1 /early S phase was higher than that of asynchronous cells (Iwasaki et al, 1995). Moreover, studies of the relationship between cell cycle and in vitro migration have shown that an increase in lymphocyte migration occurs in G 1 phase but not in S or G 2 /M phases (Wilkinson 1986;Ratner et al, 1988;Masuyama et al, 1992).…”

Divide or Conquer: Cell Cycle Regulation of Invasive Behavior

“…Reuse of developmental transcription factors in cancer is common [61]: in osteosarcomas, the transcription factor RUNX1 drives the expression of MMP9, a pro-metastatic gene, and is specifically expressed in the G1 phase of the cell cycle [71]. Additionally, hepatocellular carcinoma cells invade during the G1 phase of the cell cycle [72]. Thus, it appears that EMT-like behavior from multiple cancer types may be linked to G1/G0 cell cycle arrest.…”