A panel of human lung carcinoma lines: Establishment, properties and common characteristics

Abstract

Summary A panel of human lung carcinoma lines representing the four main histological types (squamous, small-cell, large-cell and adeno-carcinoma), and derived from both primary and metastatic sites, has been established in xenograft and in tissue culture. The highest take rates were achieved when biopsy specimens were obtained from large tumour masses and cultured lines were most readily established after preliminary passages as xenografts. The established lines exhibited an overlapping spectrum of biochemical and morphological characteristics, and showed a tendency to change from one cell type to another, in keeping with the concept of a common endodermal cell of origin. Radiation resistance appeared to be related to the large-cell phenotype.The World Health Organisation (1981) recognises four main histological types of lung cancer, with differing patterns of clinical and biological behaviour, and varying prognostic and therapeutic implications. The most important distinctions are between small-cell and non-small-cell carcinomas, the former possessing neuroendocrine properties and relative therapeutic sensitivity and the latter, features more typical of tissues of endodermal origin and with greater resistance to treatment. Since the first reported derivation of a small-cell carcinoma line in tissue culture (Oboshi et al., 1971), a number of cell lines have been established, particularly from small-cell carcinoma, and these have been the subject of extensive investigation of the biological properties of the different tumour types. A variety of phenotypic properties have been studied, including the expression of intermediate filaments, neural enzymes and hormones, and growth characteristics and requirements. As yet it has not been possible to attribute any differences in therapeutic sensitivity directly to these biological properties but they may relate to the observed differences in clinical behaviour and therefore warrant further study.The panel of lines described here was established in order to investigate the interrelationships of the different cell types, to determine growth requirements and therapeutic sensitivity, and to see whether any relationship to clinical sensitivity could be derived. A particular effort was made to obtain material from primary tumours, as the majority of lines previously studied have been derived from metastatic lesions (e.g. Carney et al., 1985). Materials and methods SpecimensTumour samples were obtained from patients undergoing diagnostic or therapeutic procedures, and transferred to the laboratory in cold tissue culture medium (Ham's F12). Solid specimens obtained at thoracotomy or removal of subcutaneous metastases were chopped into small fragments and implanted subcutaneously into male athymic nude mice (BALB/c). Tumour fragments were also disaggregated into single-cell suspensions using an enzyme mixture consisting of pronase (Calbio-Behring), DNase (Sigma) and collagenase (Boehringer-Mannheim), at 0.5, 0.2 and 0.2mg ml-in serum-free medium respectively, prior to placing in...

Experimental and clinical studies with somatostatin analogue octreotide in small cell lung cancer

“…We also measured circulating levels of IGF-I. We have shown that serum IGF-I levels do not correlate with tumour bulk in patients with SCLC (Macaulay et al, 1988b) and we used this parameter not as a tumour marker but rather as a measure of the endocrine effects of octreotide, as reported in acromegaly (Lamberts et al, 1988 (Carney et al, 1985;Duchesne et al, 1987;Macaulay et al, 1987) (Miller et al, 1981) and by serial serum levels of NSE and IGF-I. Side effects were graded as mild (grade 1), moderate (2), or severe (3).…”

“…We also measured circulating levels of IGF-I. We (Carney et al, 1985;Duchesne et al, 1987;Macaulay et al, 1987) and were cultured in RPMI 1640 medium with 5% foetal calf serum (FCS). For establishment of xenografts, 2-5 x 106 cells were innoculated subcutaneously into the flanks of female athymic (nu/nu) mice.…”

Characterization of a new small cell lung cancer (SCLC) cell line STP54 derived from a metastatic bioptate of a combined type of SCLC with Non-SCLC component.

“…However, other studies reveal that cell lines derived in such conditions are unable to grow for a long periods of time, indicating that the serum supplementation is required for establishing permanent cell lines [25]. Unfortunately, under such conditions the efficiency of establishing cell lines reaches maximally 10 per cent [2,12]. We attempted successfully to establish cell line in a serum-supplemented growth medium and after 30 passages we have regarded the cells as an established cell line.…”

Selective cytotoxic effects of a ricin A chain immunotoxin made with the monoclonal antibody SWA11 recognising a human small cell lung cancer antigen

“…All three antibodies are of the IgG2a subclass. The human classic SCLC cell line HC12 (Duchesne et al, 1987) was the gift of Dr. G. Duchesne, Institute of Cancer Research, Sutton. The human classic SCLC cell line NCI-H69 and the human lung adenocarcinoma cell line NCIIgG F(ab')2 fragment (M-1522), dithiothreitol (DTT), ophenylenediamine and thimerosal were from Sigma Chemical Co. Ltd., Poole, Dorset, England.…”