The small heat shock protein hsp27 increases invasiveness but decreases motility of breast cancer cells.
The small heat shock protein hsp27 is often expressed at high levels in clinical breast tumors; however, its biological role in this disease still remains unclear. Several laboratories have recently shown that hsp27 expression is associated with aggressive tumor behavior. We hypothesized that hsp27 may influence the metastatic tumor process since this is part of tumor 'aggressiveness'. Therefore, we stably transfected breast cancer cell lines with sense (MDA-MB-231) and antisense (MDA-MB-435) hsp27 constructs, respectively, and examined various cellular aspects associated with the metastatic process. We found that hsp27-overexpressing clones lost their protrusive morphology, but exhibited higher membrane ruffling as compared to low expressing cells. hsp27 overexpression also resulted in decreased cell motility, but invasiveness, adhesion, and growth in Matrigel were all significantly increased. Conversely, antisense suppression of hsp27 expression resulted in increased cell motility, but decreased in vitro invasiveness. The direct correlation of hsp27 levels with metastasis was confirmed by an in vivo assay measuring the number of lung metastases in mice injected with hsp27-transfected cells. Thus, we conclude that hsp27 overexpression may influence the invasive and metastatic potential of human breast cancer cells.
Lemieux
P
P
Angiotech Pharmaceuticals, Vancouver, Canada.
Oesterreich
S
S
Lawrence
J A
JA
Steeg
P S
PS
Hilsenbeck
S G
SG
Harvey
J M
JM
Fuqua
S A
SA
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D005260:Female; D006360:Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D014162:Transfection; D014183:Transplantation, Heterologous
D006360:Heat-Shock Proteins