Establishment and characterization of five human small cell lung cancer cell lines from early tumor xenografts.
Five small-cell lung carcinoma (SCLC) cell lines were established from xenografted tumor lines. These tumor lines were established after transplantation into nude mice of primary tumors or metastatic foci obtained surgically, from untreated (IRSC-2M, IRSC6M, IRSC-10M and IRSC-61M) or treated patients (IRSC-74M). They were then set-up in culture as parallel cell lines. Histologically, these tumor lines were classified as being of the classic (IRSC-2M, IRSC-10M and IRSC-61M) or intermediate type (IRSC-6M and IRSC74M). Four of these 5 SCLC cell lines grew as floating cell aggregates, while one (IRSC6M) grew as an adherent cell monolayer. Growth rates were slow (doubling times ranged between 120 and 194 h) but could be accelerated (67 to 144 h) by cultivating cells in medium mixed (v/v) with self-conditioned medium. Electron microscopical examination revealed that all SCLC cell lines contained dense core granules, characteristic of their neuroendocrine origin. These cell lines formed colonies in agarose with colony forming efficiencies ranging from 0.02-0.36%. The classic-type cell lines retained their tumorigenic capacity when re-injected intracranially into naive nude mice, whereas the intermediatetype cells did not. Cytogenetic analysis confirmed the human origin of SCLC xenografts and cultured cell lines. Various numerical and structural chromosome abnormalities were found, with deletion in the short arm of chromosome 3 being the most common (4 of the 5 cell lines). Deletions in or loss of the chromosome 10 were also observed. Oncogene expression was studied in 3 representative cell lines (IRSC-10M, IRSC-2M and IRSC-74M). L-myc was overexpressed only in IRSC-74M, while the GRP gene was overexpressed in the classic (IRSC-2M and IRSC-10M) but not in the intermediate-type cells (IRSC-74M). The Ki-ras oncogene was overexpressed in the 3 cell lines, while c-myc, N-myc, Ha-ras, N-ras, erb B2 and sis were not detected in any of them. The 3 cell lines weakly expressed the MDR1 gene, while the GST-pi gene was not expressed. These cell lines constitute a multifaceted well-characterized in vitro model for studying the biology of these phenotypically diverse cancer cells.
Institut Curie, URA 620 CNRS, Paris, France.
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D000818:Animals; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000473:pathology*; D002455:Cell Division / Q000502:physiology; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002893:Chromosomes, Human, Pair 3; D002999:Clone Cells; D005260:Female; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D008854:Microscopy, Electron; D009368:Neoplasm Transplantation; D009857:Oncogenes; D012685:Sepharose; D014183:Transplantation, Heterologous / Q000473:pathology*; D014407:Tumor Cells, Cultured
D012685:Sepharose