Polyamine Uptake by Human Colon Carcinoma Cell Line CaCo-2

Abstract

The intracellular concentrations of the polyamines are highly regulated and high polyamine concentrations are associated with rapidly proliferating cells. Hormones, nutrients and growth factors that stimulate the proliferation of the intestinal epithelium, increase the intracellular polyamine concentration mainly by activating ODC expression. Other cell types stimulated to proliferate satisfy their requirement for polyamines by increasing polyamine uptake. In the present study, we investigated polyamine uptake by a human colon carcinoma cell line, CaCo-2. Uptake of putrescine, spermidine and spermine by CaCo-2 cells was saturable and temperature dependent and all polyamines appear to share a common carrier. The carrier of differentiated cells had an apparently higher affinity and lower activity than the carrier of replicating cells. Culture of CaCo-2 cells on porous filters showed that polyamine accumulation occurred mainly through the basolateral membrane in replicating cells, while an increase in the rate of apical uptake was observed after differentiation. A significant increase in polyamine uptake and in ODC expression resulted from fresh medium replacement, a well-known stimulus to proliferation; no change in uptake occurred after ODC inhibition by DFMO. We conclude that CaCo-2 cells are able to increase their polyamine concentration by both enhanced synthesis and increased polyamine uptake.

The mechanisms by which polyamines accelerate tumor spread

“…In vitro experiments showed that cultured cells take up polyamines from their surroundings [34,35]. In blood circulation, the majority of polyamines are contained in blood cells, especially in red and white blood cells, and therefore increases in blood polyamine concentration indicate concurrent increases in polyamine levels in blood cells [36].…”

Pharmacological characteristics of the specific transporter for the endogenous cell growth inhibitor agmatine in six tumor cell lines

“…However, in experimental models of human cancer in vitro and in vivo, the specific inhibitor of ODC α-difluoromethylornithine exerted an antiproliferative effect only after combined administration with an inhibitor of polyamine uptake from extracellular sources because a characteristic feature of cancer cells is their increase in the uptake of polyamines from their environment [5,13].…”

Polyamines interact with DNA as molecular aggregates

“…Caco‐2 cells, derived from a human colon carcinoma, after confluence spontaneously differentiate assuming morphological and functional features similar to those of the small intestinal enterocytes. This cell line represents a useful in vitro model for studying the mechanisms involved in polyamine‐dependent cell replication [6,7]. Gastrin, a powerful mitogen for gastro‐intestinal cells, stimulates the growth of Caco‐2 cells and increases the intracellular concentration of polyamines promoting both their endogenous synthesis and their uptake [7].…”