M. Lacroix et al., EFFECTS OF SECRETORY PRODUCTS OF BREAST-CANCER CELLS ON OSTEOBLAST-LIKE CELLS, Breast cancer research and treatment, 38(2), 1996, pp. 209-216
The pathogenesis of breast cancer-induced osteolysis remains largely u
nknown. To evaluate the potential role of osteoblasts as target cells
during this process, we incubated SaOS-2 human osteoblast-like cells (
OBL) with culture media conditioned by proliferative (PM, 'Proliferati
on Media') or confluent (CfM, 'Confluence Media') MCF-7 human breast c
ancer cells. CfM decreased the growth of OBL by 26% (P < 0.01) while P
M was without significant effect on this parameter. In contrast, both
PM and CfM obtained from MCF-7 cultures increased the cyclic AMP (cAMP
) response of OBL to the osteolytic agents PTH (10(-8) M) and PTH-rela
ted peptide (PTHrP, 10(-8) M) by a factor of about 3 (P < 0.001), and
to prostaglandin E(2) (PGE(2), 10(-6) M) by a factor of about 2 (P < 0
.01). No significant modulation of OBL growth or sensitivity to PTH, P
THrP, or PGE2 was induced by media obtained from HBL-100 non-malignant
immortalized breast epithelial cell cultures. 17 beta-estradiol (E(2)
, 10(-8) M) and the antiestrogen tamoxifen (Tam, 10(-7) M) added for 4
8 h to MCF-7 cultures before collecting conditioned media attenuated a
nd potentiated, respectively, the PM- but not the CfM-induced increase
in the response of OBL to PTH or PTHrP. Along the same line, the addi
tion to MCF-7 conditioned media of a polyclonal anti-transforming grow
th factor-beta (TGF-beta) antibody attenuated by about 25% (P < 0.01)
the PM-induced increase in OBL response to PTH and PTHrP while abrogat
ing the modulatory effects of E(2) and Tam on that response. Together,
our results indicate that MCF-7 breast cancer cells secrete factors w
hich inhibit the growth of OBL and increase their sensitivity to vario
us osteolytic agents. TGF-beta was only partly responsible for these e
ffects, and accounts for their modulation by E(2) and Tam. The identif
ication of other osteoblast-modulatory factor(s) should contribute to
a better understanding and treatment of breast cancer-induced osteolys
is.