Abstract
A number of studies have shown that tumor cells fuse with other tumor and non-tumor cells. In the present study on tumor cell lines derived from glioblastoma, breast cancer, and melanoma, we estimated the frequency of fusion between tumor cells by establishing the fraction of cells with whole tumor-genome duplication in each cell line. Together with this, the capacity of the tumor cell lines to spread through a basement membrane scaffold was assessed, in order to test the hypothesis that pericellular proteolysis by enzymatic release in the spaces of intercellular contact could account for differences in the fusogenicity of tumor cells. The difference in invasiveness between the cell lines accounted for their specific amount of cells with tumor-genome duplication, which, depending on the cell line analyzed, ranged from 2% to 25% of the total cells. These results support the hypothesis that cell-to-cell invasion eliciting membrane fusion causes polyploidization in tumor cells.
Highlights
The implication of aneuploidy in the initiation of the carcinogenic process has been argued in recent years [1]
Cultures were kept in a humidified incubator at 37uC, in an atmosphere of 5% CO2, in either minimum-essential medium (U87MG and fibroblasts), RPMI 1640 (MA11 and FEMX-I), or Dulbecco’s modified Eagle medium (DMEM) (MDA-MB-231), supplemented with 10% fetal bovine serum (FBS) (Atlanta Biologicals), 2 mM L-glutamine (Hyclone), and 50 U/ml penicillin plus 50 mg/ml streptomycin (Lonza). 0.05% trypsin/0.5 mM ethylenediaminetetraacetic acid in Hank’s balanced salt solution and all the tissue culture media were from Mediatech Inc
In analyses carried out on cell lines of melanoma, breast cancer, and glioblastoma, a subset of cells carrying four-fold the DNA quantity of the cells of the G0/G1 peak was noticeable in cultures harvested in the phase of exponential growth (Fig. 1)
Summary
The implication of aneuploidy in the initiation of the carcinogenic process has been argued in recent years [1]. The application of a method previously employed on glioma cells to detect cells with whole tumor-genome duplication [14] has been extended to cell lines derived from melanoma and breast tumors.
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