Abstract
Tumour cell adhesion, detachment and aggregation seem to play an important part in tumour invasion and metastasis, and numerous cell adhesion molecules are expressed by tumour cells. Several families of cell-cell adhesion molecules have been described, of which two groups are particularly well characterised, the cadherin family and the Ig superfamily member, neural cell adhesion molecule (NCAM). We investigated expression of these two adhesion molecule families in small cell lung cancer (SCLC) cell lines and xenografts by immunoblotting. Nineteen tumours established from 15 patients with SCLC were examined. All tumours but one expressed both cadherin and NCAM. The tumours expressed one, two or rarely three cadherin bands, and different combinations of two major isoforms of NCAM with M(r)'s of approximately 190,000 and 135,000. Polysialylation of NCAM, a feature characteristic of NCAM during embryonic development, which may play a role in connection with tumour invasion and metastasis, was found in 14/18 NCAM expressing SCLC tumours. Individual tumours grown as cell lines and as nude mouse xenografts showed no qualitative differences in cadherin or NCAM expression.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aletsee-Ufrecht M. C., Langley K., Rotsch M., Havemann K., Gratzl M. NCAM: a surface marker for human small cell lung cancer cells. FEBS Lett. 1990 Jul 16;267(2):295–300. doi: 10.1016/0014-5793(90)80948-i. [DOI] [PubMed] [Google Scholar]
- Andersson A. M., Moran N., Gaardsvoll H., Linnemann D., Bjerkvig R., Laerum O. D., Bock E. Characterization of NCAM expression and function in BT4C and BT4Cn glioma cells. Int J Cancer. 1991 Jan 2;47(1):124–129. doi: 10.1002/ijc.2910470122. [DOI] [PubMed] [Google Scholar]
- Behrens J., Mareel M. M., Van Roy F. M., Birchmeier W. Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell-cell adhesion. J Cell Biol. 1989 Jun;108(6):2435–2447. doi: 10.1083/jcb.108.6.2435. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berendsen H. H., de Leij L., de Vries E. G., Mesander G., Mulder N. H., de Jong B., Buys C. H., Postmus P. E., Poppema S., Sluiter H. J. Characterization of three small cell lung cancer cell lines established from one patient during longitudinal follow-up. Cancer Res. 1988 Dec 1;48(23):6891–6899. [PubMed] [Google Scholar]
- Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [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]
- Doyle L. A., Borges M., Hussain A., Elias A., Tomiyasu T. An adherent subline of a unique small-cell lung cancer cell line downregulates antigens of the neural cell adhesion molecule. J Clin Invest. 1990 Dec;86(6):1848–1854. doi: 10.1172/JCI114915. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Engelholm S. A., Spang-Thomsen M., Vindeløv L. L., Brünner N., Nielsen M. H., Hirsch F., Nielsen A., Hansen H. H. Comparison of characteristics of human small cell carcinoma of the lung in patients, in vitro and transplanted into nude mice. Acta Pathol Microbiol Immunol Scand A. 1986 Sep;94(5):325–336. doi: 10.1111/j.1699-0463.1986.tb03001.x. [DOI] [PubMed] [Google Scholar]
- Engelholm S. A., Vindeløv L. L., Spang-Thomsen M., Brünner N., Tommerup N., Nielsen M. H., Hansen H. H. Genetic instability of cell lines derived from a single human small cell carcinoma of the lung. Eur J Cancer Clin Oncol. 1985 Jul;21(7):815–824. doi: 10.1016/0277-5379(85)90221-4. [DOI] [PubMed] [Google Scholar]
- Feldman L. E., Shin K. C., Natale R. B., Todd R. F., 3rd Beta 1 integrin expression on human small cell lung cancer cells. Cancer Res. 1991 Feb 15;51(4):1065–1070. [PubMed] [Google Scholar]
- Finne J. Occurrence of unique polysialosyl carbohydrate units in glycoproteins of developing brain. J Biol Chem. 1982 Oct 25;257(20):11966–11970. [PubMed] [Google Scholar]
- Geiger B., Volberg T., Ginsberg D., Bitzur S., Sabanay I., Hynes R. O. Broad spectrum pan-cadherin antibodies, reactive with the C-terminal 24 amino acid residues of N-cadherin. J Cell Sci. 1990 Dec;97(Pt 4):607–614. doi: 10.1242/jcs.97.4.607. [DOI] [PubMed] [Google Scholar]
- Hashimoto M., Niwa O., Nitta Y., Takeichi M., Yokoro K. Unstable expression of E-cadherin adhesion molecules in metastatic ovarian tumor cells. Jpn J Cancer Res. 1989 May;80(5):459–463. doi: 10.1111/j.1349-7006.1989.tb02336.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hoffman S., Edelman G. M. Kinetics of homophilic binding by embryonic and adult forms of the neural cell adhesion molecule. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5762–5766. doi: 10.1073/pnas.80.18.5762. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kibbelaar R. E., Moolenaar C. E., Michalides R. J., Bitter-Suermann D., Addis B. J., Mooi W. J. Expression of the embryonal neural cell adhesion molecule N-CAM in lung carcinoma. Diagnostic usefulness of monoclonal antibody 735 for the distinction between small cell lung cancer and non-small cell lung cancer. J Pathol. 1989 Sep;159(1):23–28. doi: 10.1002/path.1711590108. [DOI] [PubMed] [Google Scholar]
- Kyhse-Andersen J. Electroblotting of multiple gels: a simple apparatus without buffer tank for rapid transfer of proteins from polyacrylamide to nitrocellulose. J Biochem Biophys Methods. 1984 Dec;10(3-4):203–209. doi: 10.1016/0165-022x(84)90040-x. [DOI] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Lagunowich L. A., Donoso L. A., Grunwald G. B. Identification of mammalian and invertebrate analogues of the avian calcium-dependent cell adhesion protein N-cadherin with synthetic-peptide directed antibodies against a conserved cytoplasmic domain. Biochem Biophys Res Commun. 1990 Oct 15;172(1):313–320. doi: 10.1016/s0006-291x(05)80211-6. [DOI] [PubMed] [Google Scholar]
- Linnemann D., Bock E. Cell adhesion molecules in neural development. Dev Neurosci. 1989;11(3):149–173. doi: 10.1159/000111896. [DOI] [PubMed] [Google Scholar]
- Linnemann D., Raz A., Bock E. Differential expression of cell adhesion molecules in variants of K1735 melanoma cells differing in metastatic capacity. Int J Cancer. 1989 Apr 15;43(4):709–712. doi: 10.1002/ijc.2910430428. [DOI] [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]
- Moolenaar C. E., Muller E. J., Schol D. J., Figdor C. G., Bock E., Bitter-Suermann D., Michalides R. J. Expression of neural cell adhesion molecule-related sialoglycoprotein in small cell lung cancer and neuroblastoma cell lines H69 and CHP-212. Cancer Res. 1990 Feb 15;50(4):1102–1106. [PubMed] [Google Scholar]
- Owens G. C., Edelman G. M., Cunningham B. A. Organization of the neural cell adhesion molecule (N-CAM) gene: alternative exon usage as the basis for different membrane-associated domains. Proc Natl Acad Sci U S A. 1987 Jan;84(1):294–298. doi: 10.1073/pnas.84.1.294. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Patel K., Moore S. E., Dickson G., Rossell R. J., Beverley P. C., Kemshead J. T., Walsh F. S. Neural cell adhesion molecule (NCAM) is the antigen recognized by monoclonal antibodies of similar specificity in small-cell lung carcinoma and neuroblastoma. Int J Cancer. 1989 Oct 15;44(4):573–578. doi: 10.1002/ijc.2910440402. [DOI] [PubMed] [Google Scholar]
- Pettengill O. S., Sorenson G. D., Wurster-Hill D. H., Curphey T. J., Noll W. W., Cate C. C., Maurer L. H. Isolation and growth characteristics of continuous cell lines from small-cell carcinoma of the lung. Cancer. 1980 Mar 1;45(5):906–918. doi: 10.1002/1097-0142(19800301)45:5<906::aid-cncr2820450513>3.0.co;2-h. [DOI] [PubMed] [Google Scholar]
- Santoni M. J., Barthels D., Vopper G., Boned A., Goridis C., Wille W. Differential exon usage involving an unusual splicing mechanism generates at least eight types of NCAM cDNA in mouse brain. EMBO J. 1989 Feb;8(2):385–392. doi: 10.1002/j.1460-2075.1989.tb03389.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shimoyama Y., Hirohashi S., Hirano S., Noguchi M., Shimosato Y., Takeichi M., Abe O. Cadherin cell-adhesion molecules in human epithelial tissues and carcinomas. Cancer Res. 1989 Apr 15;49(8):2128–2133. [PubMed] [Google Scholar]
- Souhami R. L., Beverley P. C., Bobrow L. G., Ledermann J. A. Antigens of lung cancer: results of the second international workshop on lung cancer antigens. J Natl Cancer Inst. 1991 May 1;83(9):609–612. doi: 10.1093/jnci/83.9.609. [DOI] [PubMed] [Google Scholar]
- Spang-Thomsen M., Nielsen A., Visfeldt J. Growth curves of three human malignant tumors transplanted to nude mice. Exp Cell Biol. 1980;48(2):138–154. doi: 10.1159/000162982. [DOI] [PubMed] [Google Scholar]
- Suzuki S., Sano K., Tanihara H. Diversity of the cadherin family: evidence for eight new cadherins in nervous tissue. Cell Regul. 1991 Apr;2(4):261–270. doi: 10.1091/mbc.2.4.261. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator. Science. 1991 Mar 22;251(5000):1451–1455. doi: 10.1126/science.2006419. [DOI] [PubMed] [Google Scholar]
- Thiery J. P., Boyer B., Tucker G., Gavrilovic J., Valles A. M. Adhesion mechanisms in embryogenesis and in cancer invasion and metastasis. Ciba Found Symp. 1988;141:48–74. doi: 10.1002/9780470513736.ch4. [DOI] [PubMed] [Google Scholar]
- Tome Y., Hirohashi S., Noguchi M., Shimosato Y. Preservation of cluster 1 small cell lung cancer antigen in zinc-formalin fixative and its application to immunohistological diagnosis. Histopathology. 1990 May;16(5):469–474. doi: 10.1111/j.1365-2559.1990.tb01546.x. [DOI] [PubMed] [Google Scholar]
- Vleminckx K., Vakaet L., Jr, Mareel M., Fiers W., van Roy F. Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell. 1991 Jul 12;66(1):107–119. doi: 10.1016/0092-8674(91)90143-m. [DOI] [PubMed] [Google Scholar]
- de Leij L., Postmus P. E., Buys C. H., Elema J. D., Ramaekers F., Poppema S., Brouwer M., van der Veen A. Y., Mesander G., The T. H. Characterization of three new variant type cell lines derived from small cell carcinoma of the lung. Cancer Res. 1985 Dec;45(12 Pt 1):6024–6033. [PubMed] [Google Scholar]