Heregulin regulates the actin cytoskeleton and promotes invasive properties in breast cancer cell lines

Citation
Mm. Hijazi et al., Heregulin regulates the actin cytoskeleton and promotes invasive properties in breast cancer cell lines, INT J ONCOL, 17(4), 2000, pp. 629-641
Citations number
66
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
INTERNATIONAL JOURNAL OF ONCOLOGY
ISSN journal
10196439 → ACNP
Volume
17
Issue
4
Year of publication
2000
Pages
629 - 641
Database
ISI
SICI code
1019-6439(200010)17:4<629:HRTACA>2.0.ZU;2-I
Abstract
The metastatic process requires changes in tumor cell adhesion properties, cell motility and remodeling of the extracellular matrix. The erbB(2) proto -oncogene is overexpressed in approximately 30% of breast cancers and is a major prognostic parameter when present, in invasive disease. A ligand for the erbB(2) receptor has not yet been identified but it can be activated by heterodimerization with heregulin (HRG)-stimulated erbB(3) and erbB(4) rec eptors. The HRGs are a family of polypeptide growth factors that have been shown to play a role in embryogenesis, tumor formation, growth and differen tiation of breast cancer cells. The erbB(3) and erbB(4) receptors are invol ved in transregulation of erbB(2) signaling. The work presented here sugges ts biological roles for HRG including regulation of the actin cytoskeleton and induction of motility and invasion in breast cancer cells. HRG-expressi ng breast cancer cell lines are characterized by low erbB receptor levels a nd a high invasive and metastatic index, while those which overexpress erbB (2) demonstrate minimal invasive potential in vitro and are non-tumorigenic in vivo. Treatment of the highly tumorigenic and metastatic HRG-expressing breast cancer cell line MDA-MB-231 with an HRG-neutralizing antibody signi ficantly inhibited proliferation in culture and motility in the Boyden cham ber assay. Addition of exogenous HRG to non-invasive erbB(2) overexpressing cells (SKBr-3) at low concentrations induced formation of pseudopodia, enh anced phagocytic activity and increased chemomigration and invasion in the Boyden chamber assay. The specificity of the chemomigration response to HRG is demonstrated by inhibition with the anti-HRG neutralizing antibody. The se results suggest that either HRG can act as an autocrine or paracrine lig and to promote the invasive behavior of breast cancer cells ill vitro or th us may enhance the metastatic process in vivo.