Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1999 Mar;79(7-8):1121–1126. doi: 10.1038/sj.bjc.6690178

Mediastinal lymph node metastasis model by orthotopic intrapulmonary implantation of Lewis lung carcinoma cells in mice

Y Doki 1,2, K Murakami 1, T Yamaura 1, S Sugiyama 2, T Misaki 2, I Saiki 1
PMCID: PMC2362254  PMID: 10098745

Abstract

This study is designed to establish a pulmonary tumour model to investigate the biology and therapy of lung cancer in mice. Current methods for forming a solitary intrapulmonary nodule and subsequent metastasis to mediastinal lymph nodes are not well defined. Lewis lung carcinoma (LLC) cell suspensions were orthotopically introduced into the lung parenchyma of C57/BL6 mice via a limited skin incision without thoracotomy followed by direct puncture through the intercostal space. The implantation process was performed within approximately 50 s per mouse, and the operative mortality was less than 5%. Single pulmonary nodules developed at the implanted site in 93% of animals and subsequent mediastinal lymph node metastasis was observed in all mice that formed a lung nodule after intrapulmonary implantation. The size of tumour nodule and the weight of mediastinal lymph node increased in a time-dependent manner. The mean survival time of mice implanted successfully with LLC cells was 21 ± 2 days (range 19–24 days). Histopathological analysis revealed that no metastatic tumour was detectable in the mediastinal lymph nodes on day 11, but metastatic foci at mediastinal lymph nodes were clearly observed on days 17 and 21 after implantation. Other metastases in distant organs or lymph nodes were not observed at 21 days after the implantation. Comparative studies with intrapleural and intravenous injections of LLC cells suggest that the mediastinal lymph node metastasis by intrapulmonary impantation is due to the release of tumour cells from the primary nodule, and not due to extrapulmonary leakage of cells. An intravenous administration of cis-diamine dichrolo platinum on day 1 after tumour implantation tended to suppress the primary tumour nodule and significantly inhibited lymph node metastasis. Thus, a solitary pulmonary tumour nodule model with lymph node metastasis approximates clinical lung cancer and may provide a useful basis for lung cancer research. © 1999 Cancer Research Campaign

Keywords: lung cancer, animal model, mediastinal lymph node metastasis

Full Text

The Full Text of this article is available as a PDF (1.0 MB).

Selected References

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

  1. Bonfil R. D., Vinyals A., Bustuoabad O. D., Llorens A., Benavides F. J., Gonzalez-Garrigues M., Fabra A. Stimulation of angiogenesis as an explanation of Matrigel-enhanced tumorigenicity. Int J Cancer. 1994 Jul 15;58(2):233–239. doi: 10.1002/ijc.2910580215. [DOI] [PubMed] [Google Scholar]
  2. Brodt P. Characterization of two highly metastatic variants of Lewis lung carcinoma with different organ specificities. Cancer Res. 1986 May;46(5):2442–2448. [PubMed] [Google Scholar]
  3. Fridman R., Giaccone G., Kanemoto T., Martin G. R., Gazdar A. F., Mulshine J. L. Reconstituted basement membrane (matrigel) and laminin can enhance the tumorigenicity and the drug resistance of small cell lung cancer cell lines. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6698–6702. doi: 10.1073/pnas.87.17.6698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fridman R., Kibbey M. C., Royce L. S., Zain M., Sweeney M., Jicha D. L., Yannelli J. R., Martin G. R., Kleinman H. K. Enhanced tumor growth of both primary and established human and murine tumor cells in athymic mice after coinjection with Matrigel. J Natl Cancer Inst. 1991 Jun 5;83(11):769–774. doi: 10.1093/jnci/83.11.769. [DOI] [PubMed] [Google Scholar]
  5. Howard R. B., Chu H., Zeligman B. E., Marcell T., Bunn P. A., McLemore T. L., Mulvin D. W., Cowen M. E., Johnston M. R. Irradiated nude rat model for orthotopic human lung cancers. Cancer Res. 1991 Jun 15;51(12):3274–3280. [PubMed] [Google Scholar]
  6. Ito Y., Iwamoto Y., Tanaka K., Okuyama K., Sugioka Y. A quantitative assay using basement membrane extracts to study tumor angiogenesis in vivo. Int J Cancer. 1996 Jul 3;67(1):148–152. doi: 10.1002/(SICI)1097-0215(19960703)67:1<148::AID-IJC24>3.0.CO;2-9. [DOI] [PubMed] [Google Scholar]
  7. Jefferson M. F., Pendleton N., Faragher E. B., Dixon G. R., Myskow M. W., Horan M. A. 'Tumour volume' as a predictor of survival after resection of non-small-cell lung cancer (NSCLC) Br J Cancer. 1996 Aug;74(3):456–459. doi: 10.1038/bjc.1996.381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. McLemore T. L., Eggleston J. C., Shoemaker R. H., Abbott B. J., Bohlman M. E., Liu M. C., Fine D. L., Mayo J. G., Boyd M. R. Comparison of intrapulmonary, percutaneous intrathoracic, and subcutaneous models for the propagation of human pulmonary and nonpulmonary cancer cell lines in athymic nude mice. Cancer Res. 1988 May 15;48(10):2880–2886. [PubMed] [Google Scholar]
  9. McLemore T. L., Liu M. C., Blacker P. C., Gregg M., Alley M. C., Abbott B. J., Shoemaker R. H., Bohlman M. E., Litterst C. C., Hubbard W. C. Novel intrapulmonary model for orthotopic propagation of human lung cancers in athymic nude mice. Cancer Res. 1987 Oct 1;47(19):5132–5140. [PubMed] [Google Scholar]
  10. Morikawa K., Walker S. M., Nakajima M., Pathak S., Jessup J. M., Fidler I. J. Influence of organ environment on the growth, selection, and metastasis of human colon carcinoma cells in nude mice. Cancer Res. 1988 Dec 1;48(23):6863–6871. [PubMed] [Google Scholar]
  11. Mountain C. F. Revisions in the International System for Staging Lung Cancer. Chest. 1997 Jun;111(6):1710–1717. doi: 10.1378/chest.111.6.1710. [DOI] [PubMed] [Google Scholar]
  12. Naito S., von Eschenbach A. C., Giavazzi R., Fidler I. J. Growth and metastasis of tumor cells isolated from a human renal cell carcinoma implanted into different organs of nude mice. Cancer Res. 1986 Aug;46(8):4109–4115. [PubMed] [Google Scholar]
  13. Nakanishi R., Osaki T., Nakanishi K., Yoshino I., Yoshimatsu T., Watanabe H., Nakata H., Yasumoto K. Treatment strategy for patients with surgically discovered N2 stage IIIA non-small cell lung cancer. Ann Thorac Surg. 1997 Aug;64(2):342–348. doi: 10.1016/S0003-4975(97)00535-3. [DOI] [PubMed] [Google Scholar]
  14. Talmadge J. E., Fidler I. J. Enhanced metastatic potential of tumor cells harvested from spontaneous metastases of heterogeneous murine tumors. J Natl Cancer Inst. 1982 Oct;69(4):975–980. [PubMed] [Google Scholar]
  15. Travis W. D., Travis L. B., Devesa S. S. Lung cancer. Cancer. 1995 Jan 1;75(1 Suppl):191–202. doi: 10.1002/1097-0142(19950101)75:1+<191::aid-cncr2820751307>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]
  16. Wang H. Y., Ross H. M., Ng B., Burt M. E. Establishment of an experimental intrapulmonary tumor nodule model. Ann Thorac Surg. 1997 Jul;64(1):216–219. doi: 10.1016/s0003-4975(97)00343-3. [DOI] [PubMed] [Google Scholar]
  17. Wang X., Fu X., Hoffman R. M. A new patient-like metastatic model of human lung cancer constructed orthotopically with intact tissue via thoracotomy in immunodeficient mice. Int J Cancer. 1992 Jul 30;51(6):992–995. doi: 10.1002/ijc.2910510626. [DOI] [PubMed] [Google Scholar]
  18. Yamamura K., Kibbey M. C., Jun S. H., Kleinman H. K. Effect of Matrigel and laminin peptide YIGSR on tumor growth and metastasis. Semin Cancer Biol. 1993 Aug;4(4):259–265. [PubMed] [Google Scholar]
  19. Yano S., Nishioka Y., Izumi K., Tsuruo T., Tanaka T., Miyasaka M., Sone S. Novel metastasis model of human lung cancer in SCID mice depleted of NK cells. Int J Cancer. 1996 Jul 17;67(2):211–217. doi: 10.1002/(SICI)1097-0215(19960717)67:2<211::AID-IJC11>3.0.CO;2-E. [DOI] [PubMed] [Google Scholar]

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

RESOURCES