Cytoskeleton-associated Proteins of Human Lung Cancer Cells¹ Free

The proteins associated with the cytoskeletal framework of the major forms of lung cancer in culture were analyzed by two-dimensional gel electrophoresis of cytoskeletal framework (CSK) fractions. We have found that (a) small-cell carcinoma (SCC) lines, which differ from non-SCC lung carcinomas (adenocarcinoma, squamous carcinoma, and large-cell undifferentiated carcinoma) in morphology and growth characteristics, had a CSK composition different from that of non-SCC lines. Six separate SCC lines contained protein 1 (M_r 140,000, pl 5.2), protein 2 (M_r 140,000, pl 5.1), protein 3 (M_r 190,000, pl 7.6), and protein 4 (M_r 190,000, pl 7.5) but lacked protein 5 (M_r 80,000, pl 6.1), protein 6 (M_r 48,000, pl 5.6), and protein 7 (M_r 55,000, pl 5.5); four non-SCC lines lacked proteins 1 to 4 but contained proteins 5 to 7. Protein 7 was identified to be vimentin. (b) SCC lines, which have neuroendocrine properties, contained CSK proteins characteristic of neuroblastoma cells. Proteins 1 to 4 were found in all SCC lines, in two neuroblastoma lines, but not in other human cell lines. (c) SCC and non-SCC lines contained protein 8 (M_r 40,000, pl 5.4) and protein 9 (M_r 48,000 to 49,000, pl 6.4), which comigrate with purified keratin. These proteins were also detected in other carcinomas but not in neuroblastoma, leukemia, and fibroblast cell lines. (d) Carcinomas of the lung were distinguishable from other carcinomas by their CSK components. Nonpulmonary carcinomas lacked proteins 1 to 4 which were found in SCC lines and also lacked proteins 5 and 6 found in non-SCC lung cancer cells. The differences in the content of CSK proteins between cell lines were not due to differences in the distribution of a given protein between CSK, soluble, and nuclear fractions. These studies may have biological and clinical importance since SCC has greater metastatic capacity and therapeutic responsiveness than non-SCC lung cancers. In addition, the identification of these CSK proteins by immunohistochemical staining in human lung cancers and normal bronchial epithelium could help clarify the lineage relationships between normal bronchial epithelial cells and the different forms of lung cancer and lead to more precise diagnostic classification of lung cancer biopsy specimens.