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

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 gamma 2 chain into JHU-022-SCC cells (022), a non-invasive oral squamous cell carcinoma (OSCC) cell line which secretes Ln-5. Lysates from gamma 2 siRNA cells (022-si gamma 2) had nearly undetectable levels of the gamma 2 chain while the alpha 3 and beta 3 subunits of Ln-5 remained unchanged compared to parental and control. In conditioned medium from 022-si gamma 2 cells, the gamma 2 chain and the Ln-5 heterotrimer were barely detectable, similar to an invasive OSCC cell line. Conditioned medium from 022-si gamma 2 cells contained less alpha 3 and beta 3 subunits than both parental and control. Although the proliferation and adhesive properties of the 022-si gamma 2 cells remained similar to parental and control cells, 022-si gamma 2 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-si gamma 2 cells. Our results suggest that the Ln-5 gamma 2 chain regulates the secretion of the alpha 3 and beta 3 subunits. more importantly, suppression of Ln-5 results in a phenotype that is representative of invasive tumor cells. (c) 2005 Elsevier Inc. All rights reserved.