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American Journal of Pathology, Vol 152, 1299-1311, Copyright © 1998 by American Society for Investigative Pathology

REGULAR ARTICLES

Growth characteristics and metastatic properties of human breast cancer xenografts in immunodeficient mice

S Visonneau, A Cesano, MH Torosian, EJ Miller and D Santoli
The Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104, USA.

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.

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