Reversible squamous cell characteristics induced by vitamin A deficiency in a small cell lung cancer cell line

A cultured small cell lung cancer cell line (Lu-134-B-S) established from a xenotransplanted tumor in a nude mouse, which had originated from a primary focus of small cell lung cancer, showed morphological changes when the medium was changed from RPMI 1640 supplemented with 10% fetal calf serum to RPMI 1640 supplemented with 10% delipidized fetal calf serum. That is, it consisted of "classic" small cells in the former medium, but after eight passages in the latter medium many cells became squamous cells, possessing abundant eosinophilic cytoplasm and intercellular bridges. Immunohistochemically, they reacted to antikeratin and antiinvolucrin antibodies. Electron microscopically, well developed desmosomes and associated tonofibrils were noted, and electrophoretically, the amount of medium (Mr 57,000 and 59,000) and large-sized (Mr 67,000) keratins were found to increase with the change of the medium. These changes reversed to the original small cell morphology within 4 weeks after addition of vitamin A (retinoic acid) to the medium. These findings suggested that deficiency of vitamin A caused the change of the cell from small to squamous cell and vice versa.