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Digestive Diseases and Sciences

, Volume 49, Issue 11–12, pp 1912–1921 | Cite as

Malignant Transformation of the Mouse Anorectal Epithelium Induced by an Inoculated Human Cancer Cell Line

  • Hiroyuki Kuwano
  • Tatsuya Miyazaki
  • Soichi Tsutsumi
  • Minoru Fukuchi
  • Ken-Ichi Nomoto
  • Tatsuo Shimura
  • Erito Mochiki
  • Hiroyuki Kato
  • Takayuki Asao
  • Yasushi Toh
Article

Abstract

Four kinds of human cancer cell lines and one mouse caner cell line were inoculated into the subepithelial area of the anorectum of female nude mice. Among the cell lines, two cell lines (KATO III and Lu 135) showed the potential enforcement of atypical changes in the adjacent mouse anorectal epithelium. Moreover, the submucosal invasion of the malignant transformed cells of the mouse epithelium was demonstrated in specimens obtained from three KATO III-inoculated mice. This exciting and novel phenomenon clearly demonstrates the need to change the present general concept of a single-cell origin of cancer tissue. This valuable and novel discovery may change the basis of oncology research while also providing new ideas for projects to investigate the mechanisms of carcinogenesis from several aspects such as molecular biology, cell biology, and pathology. Moreover, the novel experimental design itself is also extremely useful as a simple model for investigating the mechanisms of oncogenesis.

malignant transformation paracrine paratransformation KATO III Lu 135 

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References

  1. 1.
    Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD: Molecular Biology of the Cell, 3rd ed. New York, London, Garland, 1994, pp 1275–1294Google Scholar
  2. 2.
    Groffen J, Stephenson JR, Heisterkamp N, de Klein A, Bartram CR, Grosveld G: Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22. Cell 36(1):93–99, 1984CrossRefPubMedGoogle Scholar
  3. 3.
    Nowell PC, Hungerford DA: A minute chromosome in human chronic granulocytic leukemia. Science 132:1497, 1960Google Scholar
  4. 4.
    Fearon ER, Hamilton SR, Vogelstein B: Clonal analysis of human colorectal tumors. Science 238(4824):193–197, 1987PubMedGoogle Scholar
  5. 5.
    Fialkow PJ: Clonal origin of human tumors. Biochim Biophys Acta 12;458(3):283–321, 1976Google Scholar
  6. 6.
    Tatematsu M, Masui T, Fukami H, et al.: Primary monoclonal and secondary polyclonal growth of colon neoplastic lesions in C3H/HeN → BALB/c chimeric mice treated with 1,2-dimethylhydrazine immunohistochemical detection of C3H strain-specific antigen and simple sequence length polymorphism analysis of DNA. Int J Cancer 66(2):234–238, 1996PubMedGoogle Scholar
  7. 7.
    Sporn MB, Todaro GJ: Autocrine secretion and malignant transformation of cells. N Engl J Med 303(15):878–880, 1980PubMedCrossRefGoogle Scholar
  8. 8.
    Kuwano H, Ueo H, Sugimachi K, Inokuchi K, Toyoshima S, Enjoji M: Glandular or mucus-secreting components in squamous cell carcinoma of the esophagus Cancer 56:514–518, 1985PubMedGoogle Scholar
  9. 9.
    Kuwano H, Matsuda H, Matsuoka H, Kai H, Okudaira Y, Sugimachi K: Intra-epithelial carcinoma concomitant with esophageal squamous cell carcinoma Cancer 59:783–787, 1987PubMedGoogle Scholar
  10. 10.
    Kuwano H, Ohno S, Matsuda H, Mori M, Sugimachi K: Serial histologic evaluation of multiple primary squamous cell carcinomas of the esophagus. Cancer 61:1635–1638, 1988PubMedGoogle Scholar
  11. 11.
    Kuwano H, Nagamatsu M, Ohno S, Matsuda H, Mori M, Sugimachi K: Coexistence of intraepithelial carcinoma and glandular differentiation in esophageal squamous cell carcinoma. Cancer 62:1568–1572, 1988PubMedGoogle Scholar
  12. 12.
    Jue SF, Bradley RS, Rudnicki JA, Varmus HE, Brown AM: The mouse Wnt-1 gene can act via a paracrine mechanism in transformation of mammary epithelial cells Mol Cell Biol 12(1):321–328, 1992PubMedGoogle Scholar
  13. 13.
    Tsutsumi S, Kuwano H, Morinaga N, Shimura T, Asao T: Animal model of para-aortic lymph node metastasis. Cancer Lett 169(1):77–85, 2001CrossRefPubMedGoogle Scholar
  14. 14.
    Motoyama T, Hojo H, Watanabe H: Comparison of seven cell lines derived from human gastric carcinomas. Acta Pathol Jpn 36(1):65–83, 1986PubMedGoogle Scholar
  15. 15.
    von Kleist S, Chany E, Burtin P, King M, Fogh J: Immunohistology of the antigenic pattern of a continuous cell line from a human colon tumor. J Natl Cancer Inst 55(3):555–560, 1975PubMedGoogle Scholar
  16. 16.
    Matozaki T, Sakamoto C, Matsuda K, et al.: Missense mutations and a deletion of the p53 gene in human gastric cancer Biochem Biophys Res Commun 182(1):215–223, 1992PubMedGoogle Scholar
  17. 17.
    Fujita T, Kiyama M, Tomizawa Y, Kohno T, Yokota J: Comprehensive analysis of p53 gene mutation characteristics in lung carcinoma with special reference to histological subtypes. Int J Oncol 15(5):927–934, 1999PubMedGoogle Scholar
  18. 18.
    Tsuruo T, Yamori T, Naganuma K, Tsukagoshi S, Sakurai Y: Characterization of metastatic clones derived from a metastatic variant of mouse colon adenocarcinoma 26. Cancer Res 43(11):5437–5442, 1983PubMedGoogle Scholar
  19. 19.
    Miyazaki T, Kato H, Shitara Y, et al.: Mutation and expression of the metastasis suppressor gene KAII in esophageal squamous cell carcinoma. Cancer 89(5):955–962, 2000CrossRefPubMedGoogle Scholar
  20. 20.
    Kuwano H, Saeki H, Kawaguchi H, et al.: Proliferative activity of cancer cells in front and center areas of carcinoma in situ and invasive sites of esophageal squamous-cell carcinoma. Int J Cancer 78(2):149–152, 1998CrossRefPubMedGoogle Scholar
  21. 21.
    Chun YS, Lindor NM, Smyrk TC, et al.: Germline E-cadherin gene mutations: Is prophylactic total gastrectomy indicated? Cancer 92(1):181–187, 2001CrossRefPubMedGoogle Scholar
  22. 22.
    Huntsman DG, Carneiro F, Lewis FR, et al.: Early gastric cancer in young, asymptomatic carriers of germ-line E-cadherin mutations N Engl J Med 344(25):1904–1909, 2001PubMedGoogle Scholar
  23. 23.
    Matsui K, Kitagawa M, Miwa A, Kuroda Y, Tsuji M: Small cell carcinoma of the stomach: A clinicopathologic study of 17 cases. Am J Gastroenterol 86(9):1167–1175, 1991PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2004

Authors and Affiliations

  • Hiroyuki Kuwano
    • 1
  • Tatsuya Miyazaki
    • 1
  • Soichi Tsutsumi
    • 1
  • Minoru Fukuchi
    • 1
  • Ken-Ichi Nomoto
    • 1
  • Tatsuo Shimura
    • 1
  • Erito Mochiki
    • 1
  • Hiroyuki Kato
    • 1
  • Takayuki Asao
    • 1
  • Yasushi Toh
    • 2
  1. 1.Department of General Surgical Science (Surgery I)Gunma University Graduate School of MedicineMaebashiJapan
  2. 2.Department of Gastroenterologic SurgeryNational Kyushu Cancer CenterJapan

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