Establishment of a clonal cell line producing granulocyte colony-stimulating factor and parathyroid hormone-related protein from a lung cancer patient with leukocytosis and hypercalcemia.

Squamous cell lung carcinoma cells obtained from a patient who presented with leukocytosis and hypercalcemia were transplanted into nude mice and a serially transplantable cell line, OKa-N-1, was established. The nude mice transplanted with OKa-N-1 cells displayed leukocytosis and hypercalcemia. Serum levels of granulocyte colony-stimulating factor (G-CSF) and parathyroid hormone-related protein (PTHrP) were both elevated in these mice. In vitro cultivation of this tumor cell line gave rise to a clonal cell line, OKa-C-1. Nude mice transplanted with the OKa-C-1 cell line also showed leukocytosis and hypercalcemia with high serum G-CSF and PTHrP levels. The culture supernatant of OKa-C-1 contained high levels of G-CSF and PTHrP. Immunohistochemical studies showed the expression of PTHrP in OKa-C-1 cells. Reverse transcription polymerase chain reaction revealed the presence of G-CSF and PTHrP mRNA in this cell line. Dexamethasone treatment inhibited the transcription of G-CSF and PTHrP genes. This new human squamous carcinoma cell line, OKa-C-1, would be useful for studying the mechanism of simultaneous production of G-CSF and PTHrP and their control in cancer patients with leukocytosis and hypercalcemia.