Genetic instability of cell lines derived from a single human small cell carcinoma of the lung

Engelholm, Svend A.; Vindeløv, Lars L.; Spang‐Thomsen, Mogens; Brünner, Nils; Tommerup, Niels; Nielsen, Merete Folmer; Hansen, Heine H.

doi:10.1016/0277-5379(85)90221-4

Cited by 48 publications

(38 citation statements)

References 22 publications

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“…This tumor was established in vitro and in vivo in nude mice by cloning from a heterogeneous cell line originating from a lymph node metastasis of the intermediate type of SCCL (8). The cellular DNA content was determined by flow cytometric DNA analysis (see below); DNA index = 1.3.…”

Section: Cph Sccl 054bmentioning

confidence: 99%

Chemosensitivity of human small cell carcinoma of the lung detected by flow cytometric DNA analysis of drug‐induced cell cycle perturbations in vitro

Engelholm

Spang‐Thomsen

Vindeløv³

et al. 1986

Cytometry

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A method based on detection of drug-induced cell cycle perturbation by flow cytometric DNA analysis has previously been described in Ehrlich ascites tumors as a way to estimate chemosensitivity. The method is extended to test human small-cell carcinoma of the lung. Three tumors with different sensitivities to melphalan in nude mice were used. Tumors were disaggregated by a combined mechanical and enzymatic method and thereafter have incubated with different doses of melphalan. After incubation the cells were plated in vitro on agar, and drug induced cell cycle changes were monitored by flow cytometric DNA analysis. Melphalan produced a dose-related S phase accumulation in the two sensitive tumors, whereas no changes in the cell cycle distribution were found in the resis- In vitro tests, especially the human tumor cloning assay (12,13), have been increasingly used to optimize treatment of malignant diseases andor to test new and more potent non-cross-resistant drugs. However, the human tumor cloning assay is time-consuming and requires 2-3 wk before conclusive results are available. Furthermore, the method does not allow one to test how representative the growing cells are. In search of a faster technique to detect chemosensitivity, a method based on measurements of drug-induced cell cycle perturbations was examined in experimental tumors (5). This in vitro flow cytometry assay was found to be able to detect sensitivity to adriamycin in Ehrlich ascites tumors.The object of the present study was to determine whether the in vitro cell cycle perturbation assay could be extended to test the chemosensitivity of human solid tumors. This demands a valid procedure to disaggregate the solid tumors into single cell suspensions representative of the original tumors. Three heterotransplanted human small-cell carcinomas of the lung (SCCL) were selected for this study because of their different sensitivities to melphalan (9). The tumors were disaggregated by a combined mechanical and enzymatic method (7).Subsequently the cells were incubated in vitro with different doses of melphalan; flow cytometric DNA analysis was used to monitor drug-induced cell cycle pertubations.The results showed that melphalan induced dose-related S phase accumulations in two sensitive tumors, whereas no cell cycle changes were found in a resistant tumor. Furthermore, the size of the S phase accumulation in vitro reflected the previously found in vivo chemosensitivity of the tumors. Thus, the results suggest that the flow cytometry method applied on disaggregated tumor cells may be extended to sensitivity testing of human tumors in general, including screening for new agents. MATERIALS AND METHODS Tumors

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Section: Cph Sccl 054bmentioning

confidence: 99%

Chemosensitivity of human small cell carcinoma of the lung detected by flow cytometric DNA analysis of drug‐induced cell cycle perturbations in vitro

Engelholm

Spang‐Thomsen

Vindeløv³

et al. 1986

Cytometry

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“…CPH-54A and CPH-54B are in vitro established subclones of the same original tumour (Engelholm et al, 1985). were established from the same patient during longitudinal follow-up (Berendsen et al, 1988 (Moolenaar et al, 1990); the specificity of this antibody has been described previously (Rasmussen et al, 1983).…”

mentioning

confidence: 99%

Expression of cadherin and NCAM in human small cell lung cancer cell lines and xenografts

Rygaard

Møller²,

Bock³

et al. 1992

Br J Cancer

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“…in vitro established subclones of the same original tumour (Engelholm et al, 1985), and CPH-136A and CPH-136B were established from the same patient before and after chemotherapy, respectively. GLC-14, were established from the same patient during longitudinal follow-up (Berendsen et al, 1988), the same was the case for GLC-26 and GLC-28.…”

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confidence: 99%

Expression of the proto-oncogenes c-met and c-kit and their ligands, hepatocyte growth factor/scatter factor and stem cell factor, in SCLC cell lines and xenografts

Rygaard¹,

Nakamura²,

Spang‐Thomsen³

1993

Br J Cancer

143

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We examined a panel of 25 small cell lung cancer (SCLC) cell lines and nude mouse xenografts for expression of the proto-oncogenes c-met and c-kit, and for expression of the corresponding ligands, hepatocyte growth factor (HGF) (also known as scatter factor (SF)), and stem cell factor (SCF), respectively. Expression of mRNA was detected by Northern blotting, and c-met and c-kit protein expression was detected by Western blotting and immunocytochemistry. c-met and c-kit mRNA was expressed in 22 of the examined cell lines or xenografts, and coexpression of the two proto-oncogenes was observed in 20 tumours. Expression of c-met and c-kit protein paralleled in the mRNA expression. HGF/SF mRNA was expressed in two of the examined tumours, and only one of these also expressed the c-met proto-oncogene. SCF mRNA was expressed in 19 of the examined tumours, and in 18 of these coexpression of c-kit and SCF was present. The high percentage of SCLC tumours expressing c-met and c-kit indicates that these proto-oncogenes may have an important function in this disease. The rare coexpression of c-met and HGF/SF is evidence that an autocrine regulatory pathway is not present for this receptor/ligand system in SCLC, while the frequent coexpression of c-kit and SCF indicates that this receptor/ligand system may have an autocrine function in SCLC. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6

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Genetic instability of cell lines derived from a single human small cell carcinoma of the lung

Cited by 48 publications

References 22 publications

Chemosensitivity of human small cell carcinoma of the lung detected by flow cytometric DNA analysis of drug‐induced cell cycle perturbations in vitro

Chemosensitivity of human small cell carcinoma of the lung detected by flow cytometric DNA analysis of drug‐induced cell cycle perturbations in vitro

Expression of cadherin and NCAM in human small cell lung cancer cell lines and xenografts

Expression of the proto-oncogenes c-met and c-kit and their ligands, hepatocyte growth factor/scatter factor and stem cell factor, in SCLC cell lines and xenografts

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