Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1994 Apr;69(4):777–783. doi: 10.1038/bjc.1994.147

Transforming growth factor beta 1 secreted from scirrhous gastric cancer cells is associated with excess collagen deposition in the tissue.

K Mahara 1, J Kato 1, T Terui 1, R Takimoto 1, M Horimoto 1, T Murakami 1, Y Mogi 1, N Watanabe 1, Y Kohgo 1, Y Niitsu 1
PMCID: PMC1968800  PMID: 8142266

Abstract

To explore the mechanism of increased collagen deposition in scirrhous carcinoma of the stomach, an attempt was made to define the role of transforming growth factor beta 1 (TGF-beta 1), secreted from tumour cells, as a possible humoral factor which functions in a paracrine manner to stimulate the production of collagen in regional fibroblasts. Immunohistochemical staining revealed that tumour cells in scirrhous carcinomas were generally stained more intensively than those in other types of carcinomas. On Northern blot analysis the tumour cells established from scirrhous carcinoma (KATO-III, OCUM-1 and HSC-39) exhibited relatively strong signals compared with those from non-scirrhous carcinoma (MKN-28 and MKN-45). In the culture media of scirrhous carcinoma cells, the active form of TGF-beta 1 was detected, while in those of the non-scirrhous carcinoma cells the latent form was demonstrated by both colony and radioreceptor assays. The culture medium from KATO-III showed strong stimulating activity of collagen synthesis in fibroblasts, and this activity was partially neutralised by an anti-TGF-beta 1 antibody. These results suggest that tumour cells in scirrhous carcinoma produce more active-form TGF-beta 1 than does non-scirrhous carcinoma and thus is partially responsible for the observed enhanced collagen deposition in the region.

Full text

PDF
777

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Assoian R. K., Komoriya A., Meyers C. A., Miller D. M., Sporn M. B. Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization. J Biol Chem. 1983 Jun 10;258(11):7155–7160. [PubMed] [Google Scholar]
  2. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  3. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  4. Frolik C. A., Wakefield L. M., Smith D. M., Sporn M. B. Characterization of a membrane receptor for transforming growth factor-beta in normal rat kidney fibroblasts. J Biol Chem. 1984 Sep 10;259(17):10995–11000. [PubMed] [Google Scholar]
  5. Goldberg D. A. Isolation and partial characterization of the Drosophila alcohol dehydrogenase gene. Proc Natl Acad Sci U S A. 1980 Oct;77(10):5794–5798. doi: 10.1073/pnas.77.10.5794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Heine U., Munoz E. F., Flanders K. C., Ellingsworth L. R., Lam H. Y., Thompson N. L., Roberts A. B., Sporn M. B. Role of transforming growth factor-beta in the development of the mouse embryo. J Cell Biol. 1987 Dec;105(6 Pt 2):2861–2876. doi: 10.1083/jcb.105.6.2861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hirayama D., Fujimori T., Satonaka K., Nakamura T., Kitazawa S., Horio M., Maeda S., Nagasako K. Immunohistochemical study of epidermal growth factor and transforming growth factor-beta in the penetrating type of early gastric cancer. Hum Pathol. 1992 Jun;23(6):681–685. doi: 10.1016/0046-8177(92)90325-w. [DOI] [PubMed] [Google Scholar]
  8. Ignotz R. A., Massagué J. Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J Biol Chem. 1986 Mar 25;261(9):4337–4345. [PubMed] [Google Scholar]
  9. Kubo T. [Establishment and characterization of a new gastric cancer cell line (OCUM-1), derived from Borrmann type IV tumor]. Nihon Geka Gakkai Zasshi. 1991 Oct;92(10):1451–1460. [PubMed] [Google Scholar]
  10. Miyazono K., Olofsson A., Colosetti P., Heldin C. H. A role of the latent TGF-beta 1-binding protein in the assembly and secretion of TGF-beta 1. EMBO J. 1991 May;10(5):1091–1101. doi: 10.1002/j.1460-2075.1991.tb08049.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Mizoi T., Ohtani H., Miyazono K., Miyazawa M., Matsuno S., Nagura H. Immunoelectron microscopic localization of transforming growth factor beta 1 and latent transforming growth factor beta 1 binding protein in human gastrointestinal carcinomas: qualitative difference between cancer cells and stromal cells. Cancer Res. 1993 Jan 1;53(1):183–190. [PubMed] [Google Scholar]
  12. Niitsu Y., Ito N., Kohda K., Owada M., Morita K., Sato S., Watanabe N., Kohgo Y., Urushizaki I. Immunohistochemical identification of type I procollagen in tumour cells of scirrhous adenocarcinoma of the stomach. Br J Cancer. 1988 Jan;57(1):79–82. doi: 10.1038/bjc.1988.13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Niitsu Y., Urushizaki Y., Koshida Y., Terui K., Mahara K., Kohgo Y., Urushizaki I. Expression of TGF-beta gene in adult T cell leukemia. Blood. 1988 Jan;71(1):263–266. [PubMed] [Google Scholar]
  14. O'Connor-McCourt M. D., Wakefield L. M. Latent transforming growth factor-beta in serum. A specific complex with alpha 2-macroglobulin. J Biol Chem. 1987 Oct 15;262(29):14090–14099. [PubMed] [Google Scholar]
  15. Peterkofsky B., Diegelmann R. Use of a mixture of proteinase-free collagenases for the specific assay of radioactive collagen in the presence of other proteins. Biochemistry. 1971 Mar 16;10(6):988–994. doi: 10.1021/bi00782a009. [DOI] [PubMed] [Google Scholar]
  16. Postlethwaite A. E., Smith G. N., Mainardi C. L., Seyer J. M., Kang A. H. Lymphocyte modulation of fibroblast function in vitro: stimulation and inhibition of collagen production by different effector molecules. J Immunol. 1984 May;132(5):2470–2477. [PubMed] [Google Scholar]
  17. Roberts A. B., Lamb L. C., Newton D. L., Sporn M. B., De Larco J. E., Todaro G. J. Transforming growth factors: isolation of polypeptides from virally and chemically transformed cells by acid/ethanol extraction. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3494–3498. doi: 10.1073/pnas.77.6.3494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sekiguchi M., Sakakibara K., Fujii G. Establishment of cultured cell lines derived from a human gastric carcinoma. Jpn J Exp Med. 1978 Feb;48(1):61–68. [PubMed] [Google Scholar]
  19. Terui T., Niitsu Y., Mahara K., Fujisaki Y., Urushizaki Y., Mogi Y., Kohgo Y., Watanabe N., Ogura M., Saito H. The production of transforming growth factor-beta in acute megakaryoblastic leukemia and its possible implications in myelofibrosis. Blood. 1990 Apr 1;75(7):1540–1548. [PubMed] [Google Scholar]
  20. Yanagihara K., Seyama T., Tsumuraya M., Kamada N., Yokoro K. Establishment and characterization of human signet ring cell gastric carcinoma cell lines with amplification of the c-myc oncogene. Cancer Res. 1991 Jan 1;51(1):381–386. [PubMed] [Google Scholar]
  21. Yanagihara K., Tsumuraya M. Transforming growth factor beta 1 induces apoptotic cell death in cultured human gastric carcinoma cells. Cancer Res. 1992 Jul 15;52(14):4042–4045. [PubMed] [Google Scholar]
  22. Yoshida K., Yokozaki H., Niimoto M., Ito H., Ito M., Tahara E. Expression of TGF-beta and procollagen type I and type III in human gastric carcinomas. Int J Cancer. 1989 Sep 15;44(3):394–398. doi: 10.1002/ijc.2910440303. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES