Tumor Cell-stromal Interactions in Lung Cancer

It is well known that tumors establish themselves and progress within a tissue microenvironment that includes host stromal cells and extracellular matrices. However, the impact that the composition of the

It is well known that tumors establish themselves and progress within a tissue rnicroenvironment that includes host stromal ceils and extracellular matrices. However, the impact that the composition of the extracellular matrix has on tumor cells remains unclear. We study the role of fibronectin in non-small cell lung carcinoma （NSCLC）, the most common lung cancer in the U.S. Fibronectin is a matrix glycoprotein highly expressed in acute and chronic lung disorders, particularly those related to tobacco-exposure like emphysema and fibrosis. Recognition of fibronectin by host and tumor ceils is mediated via heterodimeric receptors of the integrin family. We have found that exposure of NSCLC cells to fibronectin promotes tumor cell proliferation and survival as determined by increased thymidine incorporation and reduced apoptosis. These effects were inhibited by reagents against the integrina5β1, but not by reagents against other integrins. Further studies revealed that fibronectin stimulates NSCLC proliferation by activating intracellular signals that lead to cyclooxygenase-2 activation and secretion of prostaglandin E2 （PGE2）, a tumor mitogen.