The matrix
glycoprotein,
fibronectin, stimulates the proliferation of
non-small cell lung carcinoma in vitro through α5β1
integrin receptor-mediated signals. However, the true role of
fibronectin and its receptor in lung
carcinogenesis in vivo remains unclear. To test this, we generated mouse
Lewis lung carcinoma cells stably transfected with
short hairpin RNA shRNA targeting the α5
integrin subunit. These cells were characterized and tested in proliferation, cell adhesion, migration, and soft
agar colony formation assays in vitro. In addition, their growth and metastatic potential was tested in vivo in a murine model of
lung cancer. We found that transfected
Lewis lung carcinoma cells showed decreased expression of the α5 gene, which was associated with decreased adhesion to
fibronectin and reduced cell migration, proliferation, and colony formation when compared with control cells and cells stably transfected with α2
integrin subunit in vitro. C57BL/6 mice injected with α5-silenced cells showed lower burden of implanted
tumors, and a dramatic decrease in lung
metastases resulting in higher survival as compared with mice injected with wild-type or α2
integrin-silenced cells. These observations reveal that recognition of host- and/or
tumor-derived
fibronectin via α5β1 is important for
tumor growth both in vitro and in vivo, and unveil α5β1 as a potential target for the development of anti-
lung cancer therapies.