Extracellular matrix proteins protect small cell lung cancer cells againstapoptosis: A mechanism for small cell lung cancer growth and drug resistance in vivo

Resistance to chemotherapy is a principal problem in the treatment of small cell lung cancer (SCLC). We show here that SCLC is surrounded by an extens ive stroma of extracellular matrix (ECM) at both primary and metastatic sit es. Adhesion of SCLC cells to ECM enhances tumorigenicity and confers resis tance to chemotherapeutic agents as a result of pi integrin-stimulated tyro sine kinase activation suppressing chemotherapy-induced apoptosis. SCLC may create a specialized microenvironment, and the survival of cells bound to ECM could explain the partial responses and local recurrence of SCLC often seen clinically after chemotherapy. Strategies based on blocking pi integri n-mediated survival signals may represent a new therapeutic approach to imp rove the response to chemotherapy in SCLC.