Induction of squamous differentiation by interferon beta in a human non-small-cell lung cancer cell line.
BACKGROUND
More than 95% of lung cancers occur in the bronchi, appearing as adenocarcinoma, squamous carcinoma, large-cell and small-cell carcinoma, or mixed types. Generally, the least aggressive form is squamous cell lung cancer, suggesting the possibility that promotion of squamous cell differentiation may have therapeutic potential for non-small-cell lung cancer, a disease having no effective systemic therapy. Interferons are a group of glycoproteins with known antiproliferative effects, including the ability to induce differentiation in certain cases.


OBJECTIVE
These studies were conducted to determine whether interferon beta induces squamous cell differentiation in non-small-cell lung cancer in vitro.


METHODS
NCI-H596 adenosquamous cells were grown to confluence to maximize their differentiation potential. Growth and parameters for squamous differentiation (cross-linked envelope competence, transglutaminase activity, and relative involucrin expression) were then measured when the cells were exposed to various concentrations of interferon beta.


RESULTS
Interferon beta inhibited growth of the NCI-H596 cell line and stimulated envelope competence, involucrin expression, and type 2 transglutaminase activity. Alterations in transglutaminase activity and involucrin expression preceded induction of envelope competence and growth suppression.


CONCLUSIONS
Interferon beta suppresses the growth and stimulates markers of squamous differentiation in NCI-H596. While the mechanism(s) for such effects are unknown, the sequence of effects suggests a causal relationship between differentiation induction and subsequent growth suppression.


CONCLUSIONS
Interferon beta may have clinical usefulness in squamous differentiation strategies for the treatment of non-small-cell lung cancer. More must be learned about the mechanisms whereby interferons and other biologic agents induce differentiation, and clinical trials will be needed to determine whether in vitro results are pertinent in vivo.
Nair
S
S
Division of Medical Oncology, University of Pittsburgh School of Medicine, PA 15213-2592.
Mayotte
J
J
Lokshin
A
A
Levitt
M
M
D017209:Apoptosis / Q000187:drug effects; D018196:Carcinoma, Adenosquamous / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008565:Membrane Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D011503:Transglutaminases / Q000378:metabolism; D014407:Tumor Cells, Cultured
D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011498:Protein Precursors; C032253:involucrin; D016899:Interferon-beta; D011503:Transglutaminases