Suppression of laminin-5 expression leads to increased motility, tumorigenicity, and invasion

• Published in: Experimental cell research 2005-09, Vol.309 (1), p.198-210
• Main Authors: Yuen, Heng-Wai, Ziober, Amy F., Gopal, Pallavi, Nasrallah, Ilya, Falls, Erica M., Meneguzzi, Guerrino, Ang, Hwee-Quan, Ziober, Barry L.
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; CARCINOMAS; Cell Adhesion Molecules - antagonists & inhibitors; Cell Adhesion Molecules - genetics; Cell Line, Tumor; Cell migration; Cell Movement - genetics; CELL PROLIFERATION; Cell Transformation, Neoplastic - genetics; Down-Regulation; Extracellular matrix; Gene Expression Regulation, Neoplastic; Humans; IN VITRO; IN VIVO; INHIBITION; Invasion; Kalinin; Laminin - genetics; Laminin-5; MORPHOLOGY; Neoplasm Invasiveness - genetics; Neoplasms - etiology; Neoplasms - genetics; Neoplasms - metabolism; PHENOTYPE; RNA; RNA, Small Interfering; SECRETION; TUMOR CELLS; Tumorigenicity
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2005.05.013

Laminin-5 (Ln-5) is expressed in several human carcinomas and hypothesized to contribute to tumor invasion. To understand the role of Ln-5 in human cancers, we stably delivered small interfering RNAs (siRNAs) directed against the Ln-5 γ2 chain into JHU-022-SCC cells (022), a non-invasive oral squamous cell carcinoma (OSCC) cell line which secretes Ln-5. Lysates from γ2 siRNA cells (022-siγ2) had nearly undetectable levels of the γ2 chain while the α3 and β3 subunits of Ln-5 remained unchanged compared to parental and control. In conditioned medium from 022-siγ2 cells, the γ2 chain and the Ln-5 heterotrimer were barely detectable, similar to an invasive OSCC cell line. Conditioned medium from 022-siγ2 cells contained less α3 and β3 subunits than both parental and control. Although the proliferation and adhesive properties of the 022-siγ2 cells remained similar to parental and control cells, 022-siγ2 cells showed increased detachment and a fibroblastic morphology similar to invasive cells. Moreover, migration, in vitro invasion, and in vivo tumorigenicity were enhanced in 022-siγ2 cells. Our results suggest that the Ln-5 γ2 chain regulates the secretion of the α3 and β3 subunits. More importantly, suppression of Ln-5 results in a phenotype that is representative of invasive tumor cells.