Global effects of anchorage on gene expression during mammary carcinoma cell growth reveal role of tumor necrosis factor-related apoptosis-inducing ligand in anoikis

Anchorage-independent growth is a hallmark of tumor cells. We compared gene expression profiles of anchored and nonanchored human mammary carcinoma ce lls to study this phenomenon. In this study,,ve show that anchorage had str iking effects on cell growth and morphology but altered transcript levels f rom a limited number of genes. Only about 1% of mRNA transcripts detected i n these cells was altered by anchorage. These include genes related to amin o acid and polyamine metabolism, apoptosis, ion channels, cytoskeletal and stress proteins, transcription factors, and growth factors. Some of these m ay be crucial for the survival of transformed cells. For example, clusterin and the tumor necrosis factor-related apoptosis inducing ligand (TRAIL) we re suppressed by anchorage, which could help prevent programmed cell death of these tumor cells. In addition to suppressing TRAIL expression, anchorag e also decreased the susceptibility of these tumor cells to TRAIL-induced a poptosis as determined by poly(ADP-ribose) phosphorylase cleavage, annexin- V binding (P < 0.01), and cell cycle analysis (P < 0.0001). These data may help explain mechanisms by which anchorage prevents apoptosis of cells that would otherwise experience anoikis. Thus, genes found to be altered by thi s analysis could serve as potential targets for anticancer therapy. These f indings suggest that TRAIL may be used as a means to target circulating epi thelial tumor cells before their attachment and colonization at new sites.