Growth Characteristics and Metastatic Properties of Human Breast Cancer Xenografts in Immunodeficient Mice

Am J Pathol. 1998 May;152(5):1299-311.

Abstract

We evaluated the growth and metastatic potential of two human breast cancer cell lines and 16 patient-derived biopsy specimens, representing the most common histological types of breast carcinomas, upon subcutaneous implantation into severe combined immunodeficient (SCID) mice. The method of engraftment we used, based on implantation of intact tissue specimens and complete immunosuppression of the host, provided an easier system to grow human breast carcinoma specimens in mouse models and resulted in a 50% success rate of tumor take. No correlation was found between growth in SCID mice and pathological diagnosis, grading, or estrogen/progesterone receptor expression by the tumor biopsy specimen. Serial passage of the tumor fragments in SCID mice resulted in increased metastasis rates and more rapid emergence of a palpable tumor mass. A tumor from a patient with infiltrating ductal carcinoma, which grew aggressively and metastasized in 100% of the female SCID mice, was also successfully engrafted in 100% of nonobese diabetic (NOD)/SCID female mice, but systemic spread was minimal. Fragments of the same tumor grew in only 33% of male SCID mice with very limited metastases. A strong correlation (r = 0.997) was observed between tumor burden and the presence of soluble (serum) interleukin-2 receptor, a marker associated with a subset of human breast tumors. All together, these data indicate the usefulness of SCID/human breast tumor xenografts for measuring tumor progression and evaluating novel therapeutic approaches to breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / pathology
  • Aged
  • Animals
  • Biomarkers, Tumor / blood
  • Breast Neoplasms / blood
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Carcinoma, Ductal, Breast / blood
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / pathology*
  • Carcinoma, Lobular / blood
  • Carcinoma, Lobular / genetics
  • Carcinoma, Lobular / pathology*
  • Etoposide / administration & dosage
  • Female
  • Humans
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Lymphatic Metastasis / pathology
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Middle Aged
  • Neoplasm Transplantation
  • Polymerase Chain Reaction
  • Severe Combined Immunodeficiency / pathology*
  • Transplantation, Heterologous
  • Tumor Cells, Cultured / pathology
  • Tumor Cells, Cultured / transplantation

Substances

  • Biomarkers, Tumor
  • Etoposide