Extracellular matrix proteins protect small cell lung cancer cells against
apoptosis: A mechanism for small cell lung cancer growth and drug resistance
in vivo
Tariq Sethi1, Robert C. Rintoul1, Sarah M. Moore1, Alison C. MacKinnon1, Donald Salter2, Chin Choo1, Edwin R. Chilvers, Ian Dransfield1, Seamas C. Donnelly1, Robert Strieter3
& Christopher Haslett1
1
Respiratory Medicine Unit, Rayne Laboratory, University
of Edinburgh Medical School, Teviot Place, Edinburgh
EH8 9AG, Scotland, UK
2
Department of Pathology, University of Edinburgh Medical
School, Teviot Place, Edinburgh EH8 9AG,
Scotland, UK
3
6200 MSRB III, 1150 W. Medical Center, University of
Michigan Medical Center, Ann Arbor, Michigan
48109-0642, USA
Correspondence should be addressed to Tariq Sethi t.sethi@ed.ac.uk
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 extensive
stroma of extracellular matrix (ECM) at both primary and metastatic sites.
Adhesion of SCLC cells to ECM enhances tumorigenicity and confers resistance
to chemotherapeutic agents as a result of 1 integrin-stimulated tyrosine
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 1 integrin-mediated
survival signals may represent a new therapeutic approach to improve the response
to chemotherapy in SCLC.
1 integrin-stimulated tyrosine
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 
