Effect of phytohaemagglutinin on intestinal cell proliferation. Role of polyamines.

The polyamines, putrescine, spermidine and spermine, mediate the effects of hormones and growth factors as second messengers. They are necessary for every step of protein, RNA and DNA synthesis and are therefore essential for cell growth and proliferation. As with hormones and peptide growth factors, plant lectins which bind to cell surface receptors of the brush border membrane are powerful extraneous growth factors for the gut and as a result, by interacting with brush border epithelial receptors, induce extensive proliferation and changes in the metabolism of epithelial cells via activation of second messenger pathways. In model experiments with phytohaemagglutinin (PHA, the lectin from the kidney bean, Phaseolus vulgaris) it was shown that lectins which bind avidly to the mucosal surface induce dose- and time-dependent and fully reversible hyperplastic and hypertrophic growth of the small bowel. The resulting increase in crypt cell proliferation (CCPR) alters the gene expression in epithelial cells. These metabolic changes require vast amounts of polyamines, mostly spermidine. Thus, one of the first effects of the PHA signal is to stimulate the basolateral polyamine uptake system for the sequestration of polyamines from blood circulation in sufficient amounts to sustain the growth of the tissue. Our data indicate that the main source of polyamines to replenish those taken up by the gut is the diet. It has been shown repeatedly that, because of intensive cell proliferation, tumour growth requires large amounts of polyamines. PHA or other lectins accelerate normal metabolic reactions in a regulated way while maintaining their full reversibility and without causing irreversible aberrations. The fact that the lectin-induced growth of the gut requires large amounts of polyamines, suggests that lectins are ideal agents to limit the availability of polyamines for unwanted growth such as neoplastic proliferation of tumours. Accordingly, it may be possible to limit the availability of polyamines for tumour growth by inducing a competitive, but fully reversible, controlled growth of the gut tissue. The intensively but reversibly growing gut tissues can slow down tumour growth by sequestering polyamines and nutrients from circulation.