G. Baj et al., All-trans retinoic acid inhibits the growth of breast cancer cells by up-regulating ICAM-1 expression, J BIOL REG, 13(2), 1999, pp. 115-122
Citations number
35
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS
All-trans retinoic acid (ATRA) is currently used in clinical trials for bre
ast cancer, in virtue of its ability to inhibit cell growth and to promote
cell differentiation. Elucidation of the molecular mechanism(s) underlying
the pleiotropic pharmacological activity of ATRA is of fundamental relevanc
e for an effective use of the compound in clinics. This paper reports on th
e effects of ATRA treatment on the cell surface expression of a panel of ad
hesion molecules known to regulate the interactions between the effecters o
f the immune system and tumor targets. Results indicate that breast cancer
(BC) cell lines exposed to ATRA selectively up-modulate the surface express
ion of ICAM-1/CD54, a molecule regulating cell/cell contacts. Such effect c
ould be reproduced in all the BC cell lines analyzed, independently of thei
r hormone receptor status, indicating that estrogens and progesterone are i
rrelevant in this process. The regulatory effects on ICAM-1 expression are
time- and dose-dependent and reversible. Moreover, other differentiating an
d proliferating agents comparatively tested, e.g. dimethyl sulfoxide, estra
diol or dexamethas one, are ineffective, indicating that ICAM-1 up-modulati
on is uniquely featured by ATRA. A second observation is that ATRA treated
cells are, only apparently, less sensitive to lysis by lymphocytes activate
d by IL-2, as determined by means of a standard Cr-51 release assay. In fac
t, notwithstanding this effect, a marked reduction in the ability to form c
olonies was highlighted in ATRA treated versus control lines after incubati
on with LAK. Finally, the clonogenic killing effect could be reversed using
anti-CDW mAbs as blocking tools, indicating that ICAM-1 plays a key role i
n the phenomena.