Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Oct 15;88(20):9345–9349. doi: 10.1073/pnas.88.20.9345

Models of human metastatic colon cancer in nude mice orthotopically constructed by using histologically intact patient specimens.

X Y Fu 1, J M Besterman 1, A Monosov 1, R M Hoffman 1
PMCID: PMC52711  PMID: 1924398

Abstract

There is an important need for clinically relevant animal models for human cancers. Toward this goal, histologically intact human colon-cancer specimens derived surgically from patients were implanted orthotopically to the colon or cecum of nude mice. We have observed extensive orthotopic growth in 13 of 20 cases of implanted patient colon tumors. These showed various growth patterns with subsequent regional, lymph-node, and liver metastasis, as well as general abdominal carcinomatosis. Thus, models for human colon cancer have been developed that show (i) local growth, (ii) abdominal metastasis, (iii) general abdominal carcinomatosis with extensive peritoneal seeding, (iv) lymph-node metastasis, (v) liver metastasis, and (vi) colonic obstruction. These models permit the passage of the tumors to form large cohorts. They will facilitate research into the biology of colon cancer metastatic capability and the development of new drugs active against metastatic cancer. These models may also predict the clinical course and the in vivo response to drugs of the cancer of individual patients.

Full text

PDF
9346

Images in this article

Selected References

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

  1. Ahlering T. E., Dubeau L., Jones P. A. A new in vivo model to study invasion and metastasis of human bladder carcinoma. Cancer Res. 1987 Dec 15;47(24 Pt 1):6660–6665. [PubMed] [Google Scholar]
  2. Basolo F., Fontanini G., Squartini F. Differences in progression of BALB/cfRIII and BALB/cfC3H mammary hyperplastic alveolar nodules transplanted into the gland-free fat pads of BALB/c mice. Cancer Res. 1988 Jun 1;48(11):3197–3202. [PubMed] [Google Scholar]
  3. Bogden A. E., Von Hoff D. D. Comparison of the human tumor cloning and subrenal capsule assays. Cancer Res. 1984 Mar;44(3):1087–1090. [PubMed] [Google Scholar]
  4. Bresalier R. S., Raper S. E., Hujanen E. S., Kim Y. S. A new animal model for human colon cancer metastasis. Int J Cancer. 1987 May 15;39(5):625–630. doi: 10.1002/ijc.2910390514. [DOI] [PubMed] [Google Scholar]
  5. Dinesman A., Haughey B., Gates G. A., Aufdemorte T., Von Hoff D. D. Development of a new in vivo model for head and neck cancer. Otolaryngol Head Neck Surg. 1990 Nov;103(5 ):766–774. doi: 10.1177/019459989010300517. [DOI] [PubMed] [Google Scholar]
  6. Fidler I. J. Critical factors in the biology of human cancer metastasis: twenty-eighth G.H.A. Clowes memorial award lecture. Cancer Res. 1990 Oct 1;50(19):6130–6138. [PubMed] [Google Scholar]
  7. Fidler I. J. Rationale and methods for the use of nude mice to study the biology and therapy of human cancer metastasis. Cancer Metastasis Rev. 1986;5(1):29–49. doi: 10.1007/BF00049529. [DOI] [PubMed] [Google Scholar]
  8. Giavazzi R., Jessup J. M., Campbell D. E., Walker S. M., Fidler I. J. Experimental nude mouse model of human colorectal cancer liver metastases. J Natl Cancer Inst. 1986 Dec;77(6):1303–1308. [PubMed] [Google Scholar]
  9. Hoffman R. M. Three-dimensional histoculture: origins and applications in cancer research. Cancer Cells. 1991 Mar;3(3):86–92. [PubMed] [Google Scholar]
  10. Jessup J. M., Giavazzi R., Campbell D., Cleary K. R., Morikawa K., Hostetter R., Atkinson E. N., Fidler I. J. Metastatic potential of human colorectal carcinomas implanted into nude mice: prediction of clinical outcome in patients operated upon for cure. Cancer Res. 1989 Dec 15;49(24 Pt 1):6906–6910. [PubMed] [Google Scholar]
  11. Kozlowski J. M., Fidler I. J., Campbell D., Xu Z. L., Kaighn M. E., Hart I. R. Metastatic behavior of human tumor cell lines grown in the nude mouse. Cancer Res. 1984 Aug;44(8):3522–3529. [PubMed] [Google Scholar]
  12. Kozlowski J. M., Hart I. R., Fidler I. J., Hanna N. A human melanoma line heterogeneous with respect to metastatic capacity in athymic nude mice. J Natl Cancer Inst. 1984 Apr;72(4):913–917. [PubMed] [Google Scholar]
  13. Kyriazis A. P., DiPersio L., Michael G. J., Pesce A. J., Stinnett J. D. Growth patterns and metastatic behavior of human tumors growing in athymic mice. Cancer Res. 1978 Oct;38(10):3186–3190. [PubMed] [Google Scholar]
  14. Miller F. R., McInerney D. Epithelial component of host-tumor interactions in the orthotopic site preference of a mouse mammary tumor. Cancer Res. 1988 Jul 1;48(13):3698–3701. [PubMed] [Google Scholar]
  15. Morikawa K., Walker S. M., Jessup J. M., Fidler I. J. In vivo selection of highly metastatic cells from surgical specimens of different primary human colon carcinomas implanted into nude mice. Cancer Res. 1988 Apr 1;48(7):1943–1948. [PubMed] [Google Scholar]
  16. 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]
  17. Naito S., Giavazzi R., Walker S. M., Itoh K., Mayo J., Fidler I. J. Growth and metastatic behavior of human tumor cells implanted into nude and beige nude mice. Clin Exp Metastasis. 1987 Apr-Jun;5(2):135–146. doi: 10.1007/BF00058059. [DOI] [PubMed] [Google Scholar]
  18. Naito S., von Eschenbach A. C., Fidler I. J. Different growth pattern and biologic behavior of human renal cell carcinoma implanted into different organs of nude mice. J Natl Cancer Inst. 1987 Feb;78(2):377–385. [PubMed] [Google Scholar]
  19. 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]
  20. Soloway M. S., Nissenkorn I., McCallum L. Urothelial susceptibility to tumor cell implantation: comparison of cauterization with N-methyl-N-nitrosourea. Urology. 1983 Feb;21(2):159–161. doi: 10.1016/0090-4295(83)90013-4. [DOI] [PubMed] [Google Scholar]
  21. White A. C., Levy J. A., McGrath C. M. Site-selective growth of a hormone-responsive human breast carcinoma in athymic mice. Cancer Res. 1982 Mar;42(3):906–912. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES