Community Research and Development Information Service - CORDIS

FP5

ANTICANCER RETINOIDS Report Summary

Project ID: QLK3-CT-2002-02029
Funded under: FP5-LIFE QUALITY
Country: Italy

Effects of RA on micro-environmental stimuli promoting growth and survival of B cells

Proliferation of MCL cells is not significantly enhanced by physiologic concentrations of dexamethasone or hydrocortisone. Moreover, these steroid hormones are unable to antagonize the antiproliferative effects exerted by RA in MCL cells.

These results seem to rule out that endogenous GC could promote the growth of MCL cells, as instead observed for EBV-immortalized B lymphocytes. Moreover, 9-cis-RA sensitizes MCL cells to TRAIL-dependent apoptosis by a mechanism not involving TRAIL receptors. RA isomers, and particularly 9-cis-RA, are able to inhibit the growth promoting effect induced in primary MCL cells by CD40 activation alone or in combination with IL-4.

Immunohistochemical analysis showed that significant numbers of CD40L-expressing lymphoid cells are present in lymph node biopsies of MCL patients. These results, therefore, further strengthen the possibility that triggering of CD40 by infiltrating CD40L+ cells may continuously promote the growth of MCL cells in vivo.

On these grounds, our findings that RA inhibits basal MCL proliferation as well as MCL growth-promoting effects exerted by microenvironmental factors make these compounds highly attractive in terms of potential clinical efficacy in this setting.

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