Thesis (Ph.D.)--Chulalongkorn University, 2011

Caveolin-1 (CAV1) was reported to function in regulation of several cancer cell behaviors, such as anoikis, migration, invasion, ability to grow in detached condition, and so on. The present study aimed to investigate the underlying mechanism of anoikis resistance acquisition and its subsequent impacts on aggressive behaviors of human lung cancer cells. Anoikis-resistant H_AR1 and H_AR2 cells was generated from H460 cells, by serial cycles of culture under suspended and adherent conditions. H_AR1 and H_AR2 cells were found to have 23% and 44% increases in the degree of anoikis resistance respectively, and the cells also exhibited increasing cell proliferation, anchorage-independent growth, extracellular matrix adhesion, migration and invasion. However, H_AR1 and H_AR2 cells showed only minimal alteration in cisplatin susceptibility. This study revealed for the first time that cycles of detachment and attachment caused significant up-regulation of CAV1 through an induction of CAV1 mRNA transcription. To confirm, H_AR1 and H_AR2 cells were transfected with short hairpin ribonucleic acid (shRNA)-CAV1 plasmid and evaluated for cell behaviors. CAV1 level in the cells was significantly down-regulated and such protein reduction concomitant with increased anoikis and reduced anchorage-independent growth. Moreover, we generated lung cancer cells exhibiting various levels of cellular CAV1 by CAV1 and shRNA-CAV1 transfections, and acquisition of anoikis resistance and performed the correlation analysis. Results revealed that basal CAV1 level of these cells was positively correlated with anoikis resistance, anchorage-independent growth, migration, and invasion behaviors of the cells, whereas such CAV1 level showed minimal correlation to cisplatin sensitivity, cell adhesion, and growth in attached condition.