The XactMice: A Xenochimaeric Mouse with Tumor and Hematopoietic System Obtained from the Same Patient
Abstract
The lack of faithful animal models limits cancer research. One of the major factors is that regular animal models are a mixture of human tumor cells supported by mouse stroma cells, and this can have a major negative impact in research, particularly that aiming at unraveling the genetic basis of cancer (as this disrupts gene expression), and cancer stem cell and stroma studies. Aims: Generate a fully humanized and individualized model (XactMice) by acquiring and engrafting paired tumor and immortalized bone marrow precursors from the same patient in an immune-deficient mouse model. Our second Aim is to demonstrate the stability and authenticity of XactMice by comparing its gene expression, cancer stem cell profile, and drug sensitivity with a regular xenograft, and the patient's gene profile and outcome. Results: In the first year of funding we have 1) improved the methods for stabilized bone marrow precursor generation, enabling the use of lower amounts of initial patient cells; 2) demonstrated human tumors grow on a humanized mouse model; 3) shown that human stroma homes in to the tumor by dual DNA analyses; and 4) initiated patient material collection and processing. Impact on Cancer Research/ Patients: This project could result in establishing a seemingly ideal model for cancer research, with especial potential to unravel the interactions between tumor and stroma. The potential repercussions in our understanding of processes like angiogenesis and metastasis are profound. This work has the potential to yield high impact data and open new avenues of investigation into mechanisms and targeting of tumor dormancy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2011
- Accession Number
- ADA558754
Entities
People
- Antonio Jimeno
Organizations
- University of Colorado Boulder