Cell density modulates the metastatic aggressiveness of a mouse colon cancer cell line, colon 26.
OBJECTIVE
Although cell density in cultured cells has demonstrated several alterations in the nature of cell kinetics, the changes in the metastatic aggressiveness of cancer lines under different cell densities have not yet been studied.


METHODS
In the current study, we investigated the influence of changing the cell density of cultured cancer cells (colon 26 and B16-F10) injected into the tail vein in BALB/c mice on the metastatic activity by evaluating the number of lung metastases, and the possible mechanisms of this phenomenon were discussed based on the basis of the results of an invasion assay and a cell adhesion assay.


RESULTS
The number of metastatic nodules was significantly higher in the high-density group than in the low one in colon 26 (p < 0.005), however, this phenomenon was not seen in B16-F10. Next, we performed the same experiment by changing the environment to the opposite conditions for the cells in the low- and high-density groups, and the results showed the metastatic activities to be always higher in the high-density group. Moreover, although no difference was seen regarding the invasive activity between the high- and low-density groups, an adhesion assay showed the difference in the adhesion cell rate to be significantly higher in the high-density group especially in early period after coculture with human umbilical vein endothelial cells (HUVEC) (p < 0.05).


CONCLUSIONS
In some cell types, the metastatic activity could be altered and reversed by changing the environment, such as the cell density, during a relatively short period. As a result, the epigenetic changes of cancer cells are thus suggested to play a certain role in the malignant potentiality.
Kuwano
Hiroyuki
H
Department of General Surgical Science (Surgery I), Gunma University, Graduate School of Medicine, Maebashi, Gunma, Japan.
Miyazaki
Tatsuya
T
Tsutsumi
Soichi
S
Hirayama
Isao
I
Shimura
Tatsuo
T
Mochiki
Erito
E
Nomoto
Ken-Ichi
K
Fukuchi
Minoru
M
Kato
Hiroyuki
H
Asao
Takayuki
T
D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion; D002452:Cell Count; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003110:Colonic Neoplasms / Q000473:pathology*; D042783:Endothelial Cells; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D014162:Transfection; D014471:Umbilical Veins