Most primary cancers can be surgically removed, but many patients will die from metastatic disease months to years after initial therapy. Adjuvant therapies are increasingly tailored to exploit characteristics of the primary tumor however they usually improve the survival of less than 10% of breast cancer patients. It has been recently shown that dissemination is an early event and that disseminated cancer cells (DCC) differ genetically from the primary tumor. Therefore a model is needed which i) provides a human, autologous immune system and ii) allows the expansion of DCC, which belong to the rarest cells in the human body (1-2 cells per 106 bone marrow cells in positive patients), in order to investigate the interaction of these particular cell populations. Here we show that a humanized tumor mouse model can be established using hematopoietic stem cells (HSC) and DCC isolated from diagnostic BM-aspirates of melanoma and mammary carcinoma patients. Bone marrow samples are obtained prior to tumor resection. HSC are purified and engrafted by intra-femoral injection into NOD-scidIL2Rg-/- (NSG) mice and show long-term reconstitution (>24 weeks) of lymphoid and myeloid lineages, also upon serial transplantation. DCC enriched from diagnostic BM-aspirates or lymph node samples can be transplanted and are able to establish tumors in NSG mice, even at low cell numbers (<10 cells) in 50 to 70% of DCC-containing samples. Since human melanoma and mammary carcinomas are, in later stages, characterized by wide-spread metastasis, involving bone, lung and liver, we currently focus on whether and how the humanized immune system enables the systemic cancer spread of DCC derived tumors.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4242. doi:1538-7445.AM2012-4242