Reconstituted basement membrane (matrigel) and laminin can enhance the tumorigenicity and the drug resistance of small cell lung cancer cell lines.
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.
Fridman
R
R
Laboratory of Developmental Biology and Anomalies, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.
Giaccone
G
G
Kanemoto
T
T
Martin
G R
GR
Gazdar
A F
AF
Mulshine
J L
JL
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001485:Basement Membrane / Q000502:physiology*; D018288:Carcinoma, Small Cell / Q000473:pathology*; D002448:Cell Adhesion; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D004351:Drug Resistance; D006801:Humans; D007797:Laminin / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000502:physiology
D000970:Antineoplastic Agents; D007797:Laminin; D009842:Oligopeptides; D010456:Peptides, Cyclic