Liver colonization competence governs colon cancer metastasis

Tsong Hong Kuo, Tetsuro Kubota, Masahiko Watanabe, Toshiharu Furukawa, Tatuso Teramoto, Kyuya Ishibiki, Masaki Kitajima, A. Rahim Moossa, Sheldon Penman, Robert M. Hoffman

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77 Citations (Scopus)

Abstract

Tumors that metastasize do so to preferred target organs. To explain this apparent specificity, Paget, > 100 years ago, formulated his seed and soil hypothesis; i.e., the cells from a given tumor would 'seed' only favorable 'soil' offered by certain organs. The hypothesis implies that cancer cells must find a suitable 'soil' in a target organ-i.e., one that supports colonization-for metastasis to occur. We demonstrate in this report that ability of human colon cancer cells to colonize liver tissue governs whether a particular colon cancer is metastatic. In the model used in this study, human colon tumors are transplanted into the nude mouse colon as intact tissue blocks by surgical orthotopic implantation. These implanted tumors closely simulate the metastatic behavior of the original human patient tumor and are clearly metastatic or nonmetastatic to the liver. Both classes of tumors were equally invasive locally into tissues and blood vessels. However, the cells from each class of tumor behave very differently when directly injected into nude mouse livers. Only cells from metastasizing tumors are competent to colonize after direct intrahepatic injection. Also, tissue blocks from metastatic tumors affixed directly to the liver resulted in colonization, whereas no colonization resulted from nonmetastatic tumor tissue blocks even though some growth occurred within the tissue block itself. Thus, local invasion (injection) and even adhesion to the metastatic target organ (blocks) are not sufficient for metastasis. The results suggest that the ability to colonize the liver is the governing step in the metastasis of human colon cancer.

Original languageEnglish
Pages (from-to)12085-12089
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number26
DOIs
Publication statusPublished - 1995 Dec 19

Keywords

  • intrahepatic implantation
  • liver metastasis
  • nude mouse
  • orthotopic implantation

ASJC Scopus subject areas

  • General

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    Kuo, T. H., Kubota, T., Watanabe, M., Furukawa, T., Teramoto, T., Ishibiki, K., Kitajima, M., Moossa, A. R., Penman, S., & Hoffman, R. M. (1995). Liver colonization competence governs colon cancer metastasis. Proceedings of the National Academy of Sciences of the United States of America, 92(26), 12085-12089. https://doi.org/10.1073/pnas.92.26.12085