Loss of proliferative calcium dependence: simple in vitro indicator of tumorigenicity.

Abstract

The proliferative activities of three lines of "normal" epithelioid rat liver cells and six tumorigenic liver cell lines in the presence of a wide range of calcium concentrations were measured by a simple colony forming assay. The proliferative activities of the normal clis and, to a lesser extent, of the cells of a marginally tumorigenic line were directly proportional to the extracellular calcium concentration. The proliferative activities of the cells of the strongly tumorigenic lines, on the other hand, were either uninfluenced by or inversely proportional to the extracellular calcium concentration. Thus, the proliferative response to the extracellular calcium concentration is a sensitive indicator of the carcinogenic potential of liver cells. Extracellular calcium ions are needed for the initiation of DNA synthesis by a wide variety of cells ranging from rat hepatocytes in vivo (1-5), epithelial cells in primary cultures of mouse mammary glands (6), and several types of cultivated cells of mesenchymal origin (2)(3)(4)(5)(7)(8)(9)(10)(11)(12)(13)(14)(15) to the prokaryotic bacterium Yersinia pestis (16). On the other hand, neoplastic cells of mesenchymal origin (e.g, fibroblasts, muscle cells, and reticuloendothelial cells) need much less extracellular calcium and are able to proliferate indefinitely in low-calcium media that do not support the proliferation of their non-neoplastic counterparts (7-12, 13, 15). Extension of these observations to a clinically more important family of epithelial cells began only recently with the demonstration by Swierenga et al. (17) that neoplastic hepatocytes in primary cultures of a chemically induced transplantable rat hepatoma (Morris 5123tc) and hepatocytes of an established line (ATCC-CCL144) from another chemically induced transplantable rat hepatoma (Morris 7795) maintain their proliferative activity in a low-calcium medium much longer than do the hepatocytes in primary. cultures of fetal rat liver.In this communication we report the results of an assessment of the extracellular calcium requirements for colony formation by several "normal" and neoplastic epithelioid (i.e., epithelium-like) liver cell lines that indicates that the loss of proliferative calcium dependence is a simple, sensitive, in vitro indicator of their tumorigenic potential.

Active proliferation of Rous sarcoma virus-infected, but not normal, chicken heart mesenchymal cells in culture medium of physiological composition.

“…Similar ion lowering has been shown to arrest the proliferation of normal, but not of neoplastic, cells in studies by other investigators (14,15). By use of this chicken heart mesenchymal cell system, I have now attained an almost qualitative separation in the proliferative behavior of normal and RSV-infected cells-i.e., an in vitro autonomy effect under physiological conditions.…”

Differences in membrane electrical properties between C3H 10T1/2 mouse embryo fibroblasts and their ionizing radiation and chemically transformed counterparts

“…Perhaps, a similar mechanism is in force in transformed fibroblasts. In addition, it has also been shown that transformed cells require a lower calcium concentration than normal cells in order to survive (Swierenga et al 1978;Borek 1980). This change in the necessary calcium concentration may also be related to changes in the Na+/K + equilibrium since a number of calcium-activated potassium channels which respond to the calcium ion concentration are present in cells (Hille 1984).…”

The influence of royal jelly and human interferon-alpha (HuIFN-αN3) on proliferation, glutathione level and lipid peroxidation in human colorectal adenocarcinoma cells in vitro / Vpliv matičnega mlečka in humanega interferona-alfa (HuIFN-αN3) na proliferacijo, nivo glutationa in na preoksidacijo lipidov v humanih kolorektalnih adenokarcinomskih celicah in vitro

“…It can be concluded, that the most active was combination of RJ-F(M) and HuIFN-αN3 2:1, where the level of the GSH was 24.9±2. 4 Future experiments will show whether these GSH-and MDA-related activities of RJ-F (M), HuIFN-αN3, 10-HDA and their combinations may cause the decrease of the tumorigenicity index of different tumour cells in vitro, as previously reported in the literature (27,28), also through their tumorigenic potential. This is important for the practical use of royal jelly (10-HDA) and HuIFN-αN3 in a combination that could be of value for future development of tumour therapy based on the use of bioactive compounds.…”