INVESTIGADORES
COCCA Claudia Marcela
congresos y reuniones científicas
Título:
Action of Hexachlorobenzene on MDA-MB-231 human breast cancer cell invasion and tumour growth
Autor/es:
PONTILLO CA; ROJAS P; CHIAPPINI F; VENTURA C; COCCA C; LANARI C; KLEIMAN DL DE PISAREV; RANDI AS
Lugar:
Paris
Reunión:
Congreso; 47th Congress of the European Societies of Toxicology (Eurotox 2011); 2011
Institución organizadora:
European Societies of Toxicology
Resumen:
Hexachlorobenzene (HCB) is a widespread environmental pollutant and a
dioxin-like compound. We demonstrated that HCB stimulates cell migration of MDA-MB-231
breast cancer cells via c-Src/HER1/STAT5b and HER1/ERK1/2 signaling pathways. Increased activity
of metalloprotease-9 (MMP-9) is involved in angiogenesis, invasion, and
metastasis. Our aim was to examine HCB action on cell
invasion and MMP-9 activity in vitro,
and tumor growth and metastasis in vivo.
Cells were exposed to HCB (0, 0.005, 0.05, 0.5 and 5 μM) for 24 hours and then, cell invasion (matrigel coated transwells) and
MMP-9 activity (gelatine zymography) were assayed. To analyse tumour growth and
spontaneous metastasis, MDA-MB-231 cells (6x106) were injected s.c. into
both flanks of female athymic nude mice. After 10 days, HCB (0.3, 3, 30 mg/kg)
or vehicle were administered i.p. into nude mice and tumours were measured.
Animals were sacrificed at 30 days after treatment and lung, liver and thoracic
lymph node tissues were processed for histological analysis. HCB in vitro significantly increased cell
invasion (117%,p<0.05) at 5 μM and MMP-9 activity at
0.05, 0.5 and 5 μM (15%, 42% and 40%,p<0.001). In the mouse
xenograft assay, HCB (0.3 and 3 mg/kg) increased tumour volume (3244% and 3093%,p<0.001)
and tumour weight (1230%,p<0.05). Lung, liver and lymph node metastases were
registered in few control and treated mice, however the increase induced by HCB
was not statistically significant. Our data indicate
that HCB promotes MDA-MB-231 breast cancer growth in vivo and invasion and MMP-9 activity in vitro. More experiments are necessary
to prove the prometastatic effect of HCB in xenografts.