Reconstituted basement membrane (matrigel) and laminin can enhance the tumorigenicity and the drug resistance of small cell lung cancer cell lines

Rafael Fridman, Giuseppe Giaccone, Tomoko Kanemoto, George R. Martin, Adi F. Gazdar, James L. Mulshine

Research output: Contribution to journalArticle

204 Scopus citations

Abstract

Small cell lung cancer (SCLC) is a fatal malignancy due to its propensity to metastasize widely and to reoccur after chemotherapy in a drug-resistant form. While most SCLC cell lines are anchorage independent for growth, laminin induced the attachment of five of six SCLC cell lines tested (NCI-N417, NCI-H345, NCI-H146, NCI-H187, NCI-H510, and NCI-H209). NCI-N417 SCLC cells adopted a flattened morphology on laminin, and a classic SCLC cell line (NCI-H345) demonstrated a neuron-like appearance while the other SCLC cell lines except NCI-H187 cells, attached but did not spread. Adhesion to laminin was associated with increased resistance to several cytotoxic drugs. Matrigel, an extract of basement membrane proteins, greatly accelerated tumor growth when coinjected with SCLC cells in athymic mice. A synthetic peptide from the B1 chain of laminin, cyclic-YIGSR (Tyr-Ile-Gly-Ser-Arg), inhibited laminin-induced SCLC cell adhesion and migration in vitro and reduced the size of the tumors they formed when coinjected with matrigel and YIGSR. These results suggest that the interaction of SCLC cells with laminin and possibly with other basement membrane proteins can enhance their tumorigenicity and drug resistance.

Original languageEnglish (US)
Pages (from-to)6698-6702
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number17
Publication statusPublished - Sep 1990

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Keywords

  • Adhesion
  • Chemotherapy
  • Extracellular matrix
  • Tumor

ASJC Scopus subject areas

  • Genetics
  • General

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