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 gamma2 chain into JHU-022-SCC cells (022), a non-invasive oral squamous cell carcinoma (OSCC) cell line which secretes Ln-5. Lysates from gamma2 siRNA cells (022-sigamma2) had nearly undetectable levels of the gamma2 chain while the alpha3 and beta3 subunits of Ln-5 remained unchanged compared to parental and control. In conditioned medium from 022-sigamma2 cells, the gamma2 chain and the Ln-5 heterotrimer were barely detectable, similar to an invasive OSCC cell line. Conditioned medium from 022-sigamma2 cells contained less alpha3 and beta3 subunits than both parental and control. Although the proliferation and adhesive properties of the 022-sigamma2 cells remained similar to parental and control cells, 022-sigamma2 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-sigamma2 cells. Our results suggest that the Ln-5 gamma2 chain regulates the secretion of the alpha3 and beta3 subunits. More importantly, suppression of Ln-5 results in a phenotype that is representative of invasive tumor cells.
Yuen
Heng-Wai
HW
Department of Otorhinolaryngology: Head and Neck Surgery, Hospital of The University of Pennsylvania, 3400 Spruce Street, 5 Ravdin Building, Philadelphia, PA 19104, USA.
Ziober
Amy F
AF
Gopal
Pallavi
P
Nasrallah
Ilya
I
Falls
Erica M
EM
Meneguzzi
Guerrino
G
Ang
Hwee-Quan
HQ
Ziober
Barry L
BL
D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007797:Laminin / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009369:Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D007797:Laminin; D034741:RNA, Small Interfering; D000097794:Kalinin; C400567:LAMC2 protein, human