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Differentiation capacity of human non-small-cell lung cancer cell lines after exposure to phorbol ester
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stable in plasma than the small GRP peptides and, thus, may serve as a better indicator than GRP itself for expression of the FRP precursor in cancer cells.
v-ras(H) Induces non-small cell phenotype, with associated growth factors and receptors, in a small cell lung cancer cell line Falco JP, Baylin SB, Lupu R et al. Oncology Cenler, Johns Hopkins Medical Institutions, 424 North Bond St., Baltimore, MD 21231. JClin Invest 1990;85:1740-5. Small cell lung cancer (SCLC) tumor progression can involve partial or complete conversion to a more treatment-resistant non-small cell (NSCLC) phenotype. In a cell culture model of this phenomenon, we have previously demonstrated that insertion of the viral Harvey ras gene (v-Ha-ras) into SCLC cell lines with amplification and overexpression of the c-myc gene Induced many NSCLC phenotypic features. We now report that the v-Ha-ras gene can also induce morphologic, biochemical,andgrowthcharacteristicsconsistentwith theNSCLCphenotypein an N-myc amplified SCLC cell line, NCI-H249. We show that v-Hams has novel effects on these cells, abrogating a” SCLC-specific growth requirement forgastin-releasing peptide, and inducing mRNA expression of three NSCLC-associated growth factors and receptors, plateletderived growth factor B chain, transforming growth factor-a (TGF-cr.), and epidennal growth factor receptor (EGF-R). TGF-a secretion and EGF-R also appear, consistent with the induction of a” autocrine loop previously shown to begrowth stimulatory for NSCLC inculture. These data suggest that N-myc and v-Ha-ras represent functional classes of genes that may complementeach other in bringing about thephenotypic alterations seen during SCLC tumor progression, and suggest that such alterations might include the appearance of growth factors and receptars of potential importance for the growth of the tumor and its surrounding stroma. Analytical and quantitative cytology and histology: Small-cell-type poorly differentiated squamous cell carcinoma of the lung: Cytologic, immunohistochemical and nuclear DNA content analysis Abe S,Ogura S, Nakajima 1, MakimuraS, Kawakami Y, InoueK. First De/mrmnt of InternalMedicine, H&&lo UniversitySchool of Medicine, North IS, West 7. Sapporo, Hokkaido 060. Anal Quant Cytol Histol 1990;12:73-7. The relationship between the nuclear DNA content, the immunohistochemical findings, the clinical characteristics (tumor volume doubling time and survival) and the cytomorphologic features of small cell poorly differentiated squamous cell carcinoma of the lung was studied in te.n cases. There were no significant correlations between the immu“ohistochemical stainings for neuron-specific enolasc and keratin and the clinical characteristics in these cases. The DNA histogram patterns were classifiedas type lor type II,depcndingon thedegreeofdispersion ofvalues.Therc wasnorelationshiphetween thelmmunohistochemical findings and the DNA histogram patterns. Only the DNA histogram patterns were related to some of the clinical characteristics: patients with type 11 histograms had significantly shorter tumor volume doubling time.. than did paucnts with type 1 histograms. Such information may aid in distinguishing the small cell type of poorly differentiated squamous carcinoma from classic small cell carcinoma of the lung, with which it may he confused. Studies of the L-myc DNA polymorphism and relation to metastasis in Norwegian lung cancer patients Tefre T, Borresen A-L, AamdaI S, Bragger A. Department of Generics, Norwegian Radium Ifospital, Montebello. 0310 Oslo 3. Br J Cancer 1990;61:809-12. We studied 83 lung cancer patients and 129 controls for the EcoRl polymorphism of the L-myc gene. No association was found between the L-myc RFLP and increased risk of metastasis, either to lymph nodes or metastasis to other organs. There was no difference in survival time between the three different genotypes. The S-allele of the L-myc RFLP has been correlated to increased metastaGs in lung cancer. We found no tendency towards a higher frequency of this allele in the cohort of patients with positive family history compared to the patients with no known first dcgrec relatives with cancer. A higher frequency of the S-
allele in the adcnocarcinomas compared to other histological groups was found, although this difference was not statistically significant. No difference in the gene frequency of the L-myc RFLP was found between the lung cancer patients and the normal controls. These results are in contrast with a previous report. Possible explanations for the discrepenties are discussed.
Differentiation capacity of human non-small-cell lung cancer cell lines after exposure to phorbol ester Salge U, Kitian P, Neumann K, Elsasser H-P, Havemann K, Heidtmann H-H. University of Marburg, Department of Internal Medicine, Division of HematologylOncology, Baldingerstrasse. D-3550 Marburg. lnt J Cancer 1990;45: 1143-50. Three cell lines of squamous-cell carcinoma and 3 of large-cell carcinomaorigin were investigated for the expression ofdifferentiation markers and functional parameters (proliferation, morphology, comifiedenvelopefotmation,involucrin staining,transglutaminaseactivity, adhesiveness and migration) under normal cell culture conditions and after treatment with the tumor promoter phorbol-12-myristate-13. acetate (PMA). Although all original tumors had bee” described as poorly differentiated by histological grading, we found significant heterogeneity in the expression of differentiation markers in cell culture. A systematic grading of the cell lines became possible only after PMA stimulation. PMA generally increased expression of differentiation markers in cell lines of comparably low grades of differentiation, as indicated by dose-dependent inhibition of proliferation and cloning efficiency, induction of squamous markers, and decreased adhesiveness and cell motility. In contrast, cell lines of apparently higher differentiation by these criteria showed little response to PMA. The results presented show that the assessment of differentiation capacity by comparison of differentiation markers under normal cell culture and PMAstimulated conditions in established NSCLC cell lines allows for a refinedcellculturegrading, which might advancetheclassificationand characterization of such cell lines which, otherwise, appear to be very heterogeneous. It may also help to correlate cellular functions with various states of differentiation in vitro.
NCAM: A surface marker for human small cell lung cancer cells Aletsee-Ufrecht MC, Langley K, Rotsch M, Havemann K, Gratzl M. Abfeilung Anatomic undZellbiologie, Universitat Urn, Postfach4066, D-7900 Ulm. Febs Lett 1990;267:295-300. Immunocytochemical and immunochemical techniques were used to study tbe expression of the neural cell adhesion molecule (NCAM) by human lung cancer cell lines. Intense surface staining for NCAM was found at light and electron microscopy levels on small cell lung cancer cells. The NCAM palypcptide of M(r) 14ooO (NCAM 140) was detected by immunoblotting in all of 7 small cell lung cancer cell lines examined and in one out of two of the closely related large cell cancer celllines: itwasnotdetectedincell linesobtainedfromonepatientwith a mesothelioma, in two cases of adcnocarcinoma, nor in two cases of squamous cell cancer. In contrast, neuron-specific enolase was found by Immunoblotung in all the lung cancer cell lines tested and synaptophysin in all hut the adcnocarcinoma cell lines. These antigens were localized intraccllularly. The specific expression of NCAM 140 by human small and large ccl1 lung carcinomas suggests its potential as a diagnostic marker.
Effects of IL-1 and cortisol on B-adrenergic receptors, cell proliferation, and differentiation in cultured human A549 lung tumor cells Nakane T, Szentendrei T, Stem L. Virnmni M. Seely J, Kunos G. Laboralory of Physiologic and Pharmacologic Studies, National Instituteon Alcohol Abuse and Alcoholism,12501 WashingtonAve.. Rockville, MD 20852. J lmmunoll990;145:260-6. The effects of IL-1 and cortisol, and their interactions on the density ofi%adrenergicreceptors (BAR),cell pmliferation,and theadherenceof cells to plastic were studied in cultured human A549 lung tumor cells. The density of DAR, assayed by ‘?pindolol binding, was increased two-tothreefoldbya24-hincubationofthecellswith~-la.lL-l8,and
stable in plasma than the small GRP peptides and, thus, may serve as a better indicator than GRP itself for expression of the FRP precursor in cancer cells.
v-ras(H) Induces non-small cell phenotype, with associated growth factors and receptors, in a small cell lung cancer cell line Falco JP, Baylin SB, Lupu R et al. Oncology Cenler, Johns Hopkins Medical Institutions, 424 North Bond St., Baltimore, MD 21231. JClin Invest 1990;85:1740-5. Small cell lung cancer (SCLC) tumor progression can involve partial or complete conversion to a more treatment-resistant non-small cell (NSCLC) phenotype. In a cell culture model of this phenomenon, we have previously demonstrated that insertion of the viral Harvey ras gene (v-Ha-ras) into SCLC cell lines with amplification and overexpression of the c-myc gene Induced many NSCLC phenotypic features. We now report that the v-Ha-ras gene can also induce morphologic, biochemical,andgrowthcharacteristicsconsistentwith theNSCLCphenotypein an N-myc amplified SCLC cell line, NCI-H249. We show that v-Hams has novel effects on these cells, abrogating a” SCLC-specific growth requirement forgastin-releasing peptide, and inducing mRNA expression of three NSCLC-associated growth factors and receptors, plateletderived growth factor B chain, transforming growth factor-a (TGF-cr.), and epidennal growth factor receptor (EGF-R). TGF-a secretion and EGF-R also appear, consistent with the induction of a” autocrine loop previously shown to begrowth stimulatory for NSCLC inculture. These data suggest that N-myc and v-Ha-ras represent functional classes of genes that may complementeach other in bringing about thephenotypic alterations seen during SCLC tumor progression, and suggest that such alterations might include the appearance of growth factors and receptars of potential importance for the growth of the tumor and its surrounding stroma. Analytical and quantitative cytology and histology: Small-cell-type poorly differentiated squamous cell carcinoma of the lung: Cytologic, immunohistochemical and nuclear DNA content analysis Abe S,Ogura S, Nakajima 1, MakimuraS, Kawakami Y, InoueK. First De/mrmnt of InternalMedicine, H&&lo UniversitySchool of Medicine, North IS, West 7. Sapporo, Hokkaido 060. Anal Quant Cytol Histol 1990;12:73-7. The relationship between the nuclear DNA content, the immunohistochemical findings, the clinical characteristics (tumor volume doubling time and survival) and the cytomorphologic features of small cell poorly differentiated squamous cell carcinoma of the lung was studied in te.n cases. There were no significant correlations between the immu“ohistochemical stainings for neuron-specific enolasc and keratin and the clinical characteristics in these cases. The DNA histogram patterns were classifiedas type lor type II,depcndingon thedegreeofdispersion ofvalues.Therc wasnorelationshiphetween thelmmunohistochemical findings and the DNA histogram patterns. Only the DNA histogram patterns were related to some of the clinical characteristics: patients with type 11 histograms had significantly shorter tumor volume doubling time.. than did paucnts with type 1 histograms. Such information may aid in distinguishing the small cell type of poorly differentiated squamous carcinoma from classic small cell carcinoma of the lung, with which it may he confused. Studies of the L-myc DNA polymorphism and relation to metastasis in Norwegian lung cancer patients Tefre T, Borresen A-L, AamdaI S, Bragger A. Department of Generics, Norwegian Radium Ifospital, Montebello. 0310 Oslo 3. Br J Cancer 1990;61:809-12. We studied 83 lung cancer patients and 129 controls for the EcoRl polymorphism of the L-myc gene. No association was found between the L-myc RFLP and increased risk of metastasis, either to lymph nodes or metastasis to other organs. There was no difference in survival time between the three different genotypes. The S-allele of the L-myc RFLP has been correlated to increased metastaGs in lung cancer. We found no tendency towards a higher frequency of this allele in the cohort of patients with positive family history compared to the patients with no known first dcgrec relatives with cancer. A higher frequency of the S-
allele in the adcnocarcinomas compared to other histological groups was found, although this difference was not statistically significant. No difference in the gene frequency of the L-myc RFLP was found between the lung cancer patients and the normal controls. These results are in contrast with a previous report. Possible explanations for the discrepenties are discussed.
Differentiation capacity of human non-small-cell lung cancer cell lines after exposure to phorbol ester Salge U, Kitian P, Neumann K, Elsasser H-P, Havemann K, Heidtmann H-H. University of Marburg, Department of Internal Medicine, Division of HematologylOncology, Baldingerstrasse. D-3550 Marburg. lnt J Cancer 1990;45: 1143-50. Three cell lines of squamous-cell carcinoma and 3 of large-cell carcinomaorigin were investigated for the expression ofdifferentiation markers and functional parameters (proliferation, morphology, comifiedenvelopefotmation,involucrin staining,transglutaminaseactivity, adhesiveness and migration) under normal cell culture conditions and after treatment with the tumor promoter phorbol-12-myristate-13. acetate (PMA). Although all original tumors had bee” described as poorly differentiated by histological grading, we found significant heterogeneity in the expression of differentiation markers in cell culture. A systematic grading of the cell lines became possible only after PMA stimulation. PMA generally increased expression of differentiation markers in cell lines of comparably low grades of differentiation, as indicated by dose-dependent inhibition of proliferation and cloning efficiency, induction of squamous markers, and decreased adhesiveness and cell motility. In contrast, cell lines of apparently higher differentiation by these criteria showed little response to PMA. The results presented show that the assessment of differentiation capacity by comparison of differentiation markers under normal cell culture and PMAstimulated conditions in established NSCLC cell lines allows for a refinedcellculturegrading, which might advancetheclassificationand characterization of such cell lines which, otherwise, appear to be very heterogeneous. It may also help to correlate cellular functions with various states of differentiation in vitro.
NCAM: A surface marker for human small cell lung cancer cells Aletsee-Ufrecht MC, Langley K, Rotsch M, Havemann K, Gratzl M. Abfeilung Anatomic undZellbiologie, Universitat Urn, Postfach4066, D-7900 Ulm. Febs Lett 1990;267:295-300. Immunocytochemical and immunochemical techniques were used to study tbe expression of the neural cell adhesion molecule (NCAM) by human lung cancer cell lines. Intense surface staining for NCAM was found at light and electron microscopy levels on small cell lung cancer cells. The NCAM palypcptide of M(r) 14ooO (NCAM 140) was detected by immunoblotting in all of 7 small cell lung cancer cell lines examined and in one out of two of the closely related large cell cancer celllines: itwasnotdetectedincell linesobtainedfromonepatientwith a mesothelioma, in two cases of adcnocarcinoma, nor in two cases of squamous cell cancer. In contrast, neuron-specific enolase was found by Immunoblotung in all the lung cancer cell lines tested and synaptophysin in all hut the adcnocarcinoma cell lines. These antigens were localized intraccllularly. The specific expression of NCAM 140 by human small and large ccl1 lung carcinomas suggests its potential as a diagnostic marker.
Effects of IL-1 and cortisol on B-adrenergic receptors, cell proliferation, and differentiation in cultured human A549 lung tumor cells Nakane T, Szentendrei T, Stem L. Virnmni M. Seely J, Kunos G. Laboralory of Physiologic and Pharmacologic Studies, National Instituteon Alcohol Abuse and Alcoholism,12501 WashingtonAve.. Rockville, MD 20852. J lmmunoll990;145:260-6. The effects of IL-1 and cortisol, and their interactions on the density ofi%adrenergicreceptors (BAR),cell pmliferation,and theadherenceof cells to plastic were studied in cultured human A549 lung tumor cells. The density of DAR, assayed by ‘?pindolol binding, was increased two-tothreefoldbya24-hincubationofthecellswith~-la.lL-l8,and