The monoclonal antibody directed against gastrin releasing peptide and bombesin, 2A11, can inhibit the growth of small cell lung cancer in vitro and in vivo and intravenous administration has induced a clinical remission in a patient with relapsed small cell lung cancer.
In addition, the effect of BBI on the growth factor processing of proGRP by SCLC cells and on mRNA levels for prohormone convertase 1 and 2 (PC1 and PC2) in SCLC cells was examined.
Production of the growth factor gastrin-releasing peptide (GRP) or human bombesin has been shown to be a feature of neuroendocrine tumours of the lung, particularly small cell carcinoma, and is possibly responsible for the characteristically rapid growth of this tumour.
The effects of bombesin on three human small cell lung carcinoma cell (SCLC) lines (NCI-H69, NCI-H128, and NCI-H345) have been examined and compared to the effects of the peptide on the mouse fibroblast cell line Swiss 3T3, and the rat pituitary tumor cell line GH3W5.
Our results provide evidence for the expression of the bombesin gene in small cell carcinoma of the lung at a cellular level and show that probombesin mRNA is highly expressed in these tumors.
In the two SCLC cell lines expressing GRP we find a single transcription start site for GRP mRNA, and near this site we find four DNase I hypersensitive sites.
After multiple passages, UMC-SCLC-1 gradually changed its culture characteristics to a cell line, UMC-SCLC-1A, with morphological features of large cell anaplastic carcinoma, an altered growth pattern, decrease in calcitonin, and increase in radioresistance but retained the other biochemical markers of classic SCLC (bombesin and dopa decarboxylase production).
Examination of the structure of prepro-GRP transcripts found in SCLC reveals three types of prepro-GRP mRNA which differ in the structure of a putative GRP-associated peptide in the pro-GRP precursor.