THE SMALL HEAT-SHOCK-PROTEIN HSP27 INCREASES INVASIVENESS BUT DECREASES MOTILITY OF BREAST-CANCER CELLS

0The small heat shock protein hsp27 is often expressed at high levels in clinical breast tumors; however, its biological role in this diseas e still remains unclear. Several laboratories have recently shown that hsp27 expression is associated with aggressive tumor behavior. We hyp othesized that hsp27 may influence the metastatic tumor process since this is part of tumor 'aggressiveness'. Therefore,we stably transfecte d 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-ov erexpressing clones lost their protrusive morphology, but exhibited hi gher membrane ruffling as compared to low expressing cells. hsp27 over expression also resulted in decreased cell motility, but invasiveness, adhesion, and growth in Matrigel were all significantly increased. Co nversely, antisense suppression of hsp27 expression resulted in increa sed cell motility, but decreased in vitro Invasiveness, The direct cor relation of hsp27 levels with metastasis was confirmed by an in vivo a ssay measuring the number of lung metastases in mice injected with hsp 27-transfected cells. Thus, we conclude that hsp27 overexpression may influence the invasive and metastatic potential of human breast cancer cells.