Abstract
Controversy exists as to whether interferons usefully influence the growth of epithelial carcinomas. A small cell lung carcinoma (SCLC) cell line, WX322, has been derived which is greater than 1000-fold more sensitive to alpha-interferon (IFN) when grown in agar than other reported SCLC cell lines. The WX322 line has been characterised to prove its epithelial origin and its chemosensitivity compared with that of the NCI-H69 small cell line. The WX322 cell line expresses neuroendocrine and epithelial markers and possesses a morphology consistent with SCLC origin. A concentration of 5 IU ml-1 of IFN produced 50% inhibition of colony formation in agar in the WX322 line, whereas a concentration of greater than 10(5) IU ml-1 was required to produce a comparable effect with the NCI-H69 cell line. In contrast, WX322, possessed similar sensitivity to NCI-H69 cells when exposed to a range of cytotoxic agents. Analysis of the cell cycle indicated that IFN increased the percentage of cells in the G0/G1 phase for the WX322 cell line but increased the percentage in S phase for the NCI-H69 line. Growth of the xenograft, from which the cell line was derived, was also inhibited by IFN at doses greater than 10(5) IU/mouse/day. The WX322 cell line whether grown in agar or as a xenograft shows an unusually high sensitivity to IFN and provides an interesting model for studying mechanisms of IFN cytotoxicity to epithelial cells.
Full text
PDF






Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Allan P. M., Garson J. A., Harper E. I., Asser U., Coakham H. B., Brownell B., Kemshead J. T. Biological characterization and clinical applications of a monoclonal antibody recognizing an antigen restricted to neuroectodermal tissues. Int J Cancer. 1983 May 15;31(5):591–598. doi: 10.1002/ijc.2910310510. [DOI] [PubMed] [Google Scholar]
- Bakhanashvili M., Wreschner D. H., Salzberg S. Specific antigrowth effect of interferon on mouse cells transformed by murine sarcoma virus. Cancer Res. 1983 Mar;43(3):1289–1294. [PubMed] [Google Scholar]
- Balkwill F. R., Moodie E. M., Freedman V., Fantes K. H. Human interferon inhibits the growth of established human breast tumours in the nude mouse. Int J Cancer. 1982 Aug 15;30(2):231–235. doi: 10.1002/ijc.2910300217. [DOI] [PubMed] [Google Scholar]
- Balkwill F. R., Proietti E. Effects of mouse interferon on human tumour xenografts in the nude mouse host. Int J Cancer. 1986 Sep 15;38(3):375–380. doi: 10.1002/ijc.2910380312. [DOI] [PubMed] [Google Scholar]
- Bepler G., Carney D. N., Nau M. M., Gazdar A. F., Minna J. D. Additive and differential biological activity of alpha-interferon A, difluoromethylornithine, and their combination on established human lung cancer cell lines. Cancer Res. 1986 Jul;46(7):3413–3419. [PubMed] [Google Scholar]
- Burchell J., Durbin H., Taylor-Papadimitriou J. Complexity of expression of antigenic determinants, recognized by monoclonal antibodies HMFG-1 and HMFG-2, in normal and malignant human mammary epithelial cells. J Immunol. 1983 Jul;131(1):508–513. [PubMed] [Google Scholar]
- Carney D. N., Gazdar A. F., Bepler G., Guccion J. G., Marangos P. J., Moody T. W., Zweig M. H., Minna J. D. Establishment and identification of small cell lung cancer cell lines having classic and variant features. Cancer Res. 1985 Jun;45(6):2913–2923. [PubMed] [Google Scholar]
- Courtenay V. D., Selby P. J., Smith I. E., Mills J., Peckham M. J. Growth of human tumour cell colonies from biopsies using two soft-agar techniques. Br J Cancer. 1978 Jul;38(1):77–81. doi: 10.1038/bjc.1978.165. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fergusson R. J., Carmichael J., Smyth J. F. Human tumour xenografts growing in immunodeficient mice: a useful model for assessing chemotherapeutic agents in bronchial carcinoma. Thorax. 1986 May;41(5):376–380. doi: 10.1136/thx.41.5.376. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fonnum F. Isolation of choline esters from aqueous solutions by extraction with sodium tetraphenylboron in organic solvents. Biochem J. 1969 Jun;113(2):291–298. doi: 10.1042/bj1130291. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gazdar A. F., Carney D. N., Nau M. M., Minna J. D. Characterization of variant subclasses of cell lines derived from small cell lung cancer having distinctive biochemical, morphological, and growth properties. Cancer Res. 1985 Jun;45(6):2924–2930. [PubMed] [Google Scholar]
- Jabbar S. A., Twentyman P. R., Watson J. V. The MTT assay underestimates the growth inhibitory effects of interferons. Br J Cancer. 1989 Oct;60(4):523–528. doi: 10.1038/bjc.1989.306. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jones D. H., Bleehen N. M., Slater A. J., George P. J., Walker J. R., Dixon A. K. Human lymphoblastoid interferon in the treatment of small cell lung cancer. Br J Cancer. 1983 Mar;47(3):361–366. doi: 10.1038/bjc.1983.54. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Laduron P., Belpaire F. A rapid assay and partial purification of dopa decarboxylase. Anal Biochem. 1968 Nov;26(2):210–218. doi: 10.1016/0003-2697(68)90332-1. [DOI] [PubMed] [Google Scholar]
- Lundblad D., Lundgren E. Block of glioma cell line in S by interferon. Int J Cancer. 1981 Jun 15;27(6):749–754. doi: 10.1002/ijc.2910270604. [DOI] [PubMed] [Google Scholar]
- Makin C. A., Bobrow L. G., Bodmer W. F. Monoclonal antibody to cytokeratin for use in routine histopathology. J Clin Pathol. 1984 Sep;37(9):975–983. doi: 10.1136/jcp.37.9.975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mooi W. J., Wagenaar S. S., Schol D., Hilgers J. Monoclonal antibody 123C3 in lung tumour classification. Immunohistology of 358 resected lung tumours. Mol Cell Probes. 1988 Mar;2(1):31–37. doi: 10.1016/0890-8508(88)90041-2. [DOI] [PubMed] [Google Scholar]
- Munker M., Munker R., Saxton R. E., Koeffler H. P. Effect of recombinant monokines, lymphokines, and other agents on clonal proliferation of human lung cancer cell lines. Cancer Res. 1987 Aug 1;47(15):4081–4085. [PubMed] [Google Scholar]
- Olesen B. K., Ernst P., Nissen M. H., Hansen H. H. Recombinant interferon A (IFL-rA) therapy of small cell and squamous cell carcinoma of the lung. A phase II study. Eur J Cancer Clin Oncol. 1987 Jul;23(7):987–989. doi: 10.1016/0277-5379(87)90346-4. [DOI] [PubMed] [Google Scholar]
- Roos G., Leanderson T., Lundgren E. Interferon-induced cell cycle changes in human hematopoietic cell lines and fresh leukemic cells. Cancer Res. 1984 Jun;44(6):2358–2362. [PubMed] [Google Scholar]
- Schol D. J., Mooi W. J., van der Gugten A. A., Wagenaar S. S., Hilgers J. Monoclonal antibody 123C3, identifying small cell carcinoma phenotype in lung tumours, recognizes mainly, but not exclusively, endocrine and neuron-supporting normal tissues. Int J Cancer Suppl. 1988;2:34–40. doi: 10.1002/ijc.2910410711. [DOI] [PubMed] [Google Scholar]
- Smyth J. F., Balkwill F. R., Cavalli F., Kimchi A., Mattson K., Niederle N. E., Spiegel R. J. Interferons in oncology: current status and future directions. Eur J Cancer Clin Oncol. 1987 Jun;23(6):887–889. doi: 10.1016/0277-5379(87)90298-7. [DOI] [PubMed] [Google Scholar]
- Spurr N. K., Durbin H., Sheer D., Parkar M., Bobrow L., Bodmer W. F. Characterization and chromosomal assignment of a human cell surface antigen defined by the monoclonal antibody AUAI. Int J Cancer. 1986 Nov 15;38(5):631–636. doi: 10.1002/ijc.2910380503. [DOI] [PubMed] [Google Scholar]
- Sternberger L. A. The unlabeled antibody (PAP) method, introduction. J Histochem Cytochem. 1979 Dec;27(12):1657–1657. doi: 10.1177/27.12.392001. [DOI] [PubMed] [Google Scholar]
- Twentyman P. R., Workman P., Wright K. A., Bleehen N. M. The effects of alpha and gamma interferons on human lung cancer cells grown in vitro or as xenografts in nude mice. Br J Cancer. 1985 Jul;52(1):21–29. doi: 10.1038/bjc.1985.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vindeløv L. L., Christensen I. J., Nissen N. I. A detergent-trypsin method for the preparation of nuclei for flow cytometric DNA analysis. Cytometry. 1983 Mar;3(5):323–327. doi: 10.1002/cyto.990030503. [DOI] [PubMed] [Google Scholar]

