Genetically diverse mouse platform to xenograft cancer cells

Author:

Sargent Jennifer K.1,Warner Mark A.1,Low Benjamin E.1,Schott William H.1,Hoffert Todd1,Coleman David1,Woo Xing Yi2ORCID,Sheridan Todd23,Erattupuzha Sonia1ORCID,Henrich Philipp P.1ORCID,Philip Vivek M.1,Chuang Jeffrey H.2ORCID,Wiles Michael V.1,Hasham Muneer G.1ORCID

Affiliation:

1. The Jackson Laboratory for Mouse Genetics 1 , 600 Main Street, Bar Harbor, ME 04609 , USA

2. The Jackson Laboratory for Genomic Medicine 2 , 10 Discovery Drive, Farmington, CT 06032 , USA

3. Hartford Hospital 3 , Department of Pathology, 80 Seymour Street, Hartford, CT 06102 , USA

Abstract

ABSTRACT The lack of genetically diverse preclinical animal models in basic biology and efficacy testing has been cited as a potential cause of failure in clinical trials. We developed and characterized five diverse RAG1 null mouse strains as models that allow xenografts to grow. In these strains, we characterized the growth of breast cancer, leukemia and glioma cell lines. We found a wide range of growth characteristics that were far more dependent on strain than tumor type. For the breast cancer cell line, we characterized the spectrum of xenograft/tumor growth at structural, histological, cellular and molecular levels across each strain, and found that each strain captures unique structural components of the stroma. Furthermore, we showed that the increase in tumor-infiltrating myeloid CD45+ cells and the amount of circulating cytokine IL-6 and chemokine KC (also known as CXCL1) is associated with a higher tumor size in different strains. This resource is available to study established human xenografts, as well as difficult-to-xenograft tumors and growth of hematopoietic stems cells, and to decipher the role of myeloid cells in the development of spontaneous cancers.

Funder

Jackson Laboratory

National Cancer Institute

Linda Tallen and David Kane Educational Fund

Publisher

The Company of Biologists

Subject

General Biochemistry, Genetics and Molecular Biology,Immunology and Microbiology (miscellaneous),Medicine (miscellaneous),Neuroscience (miscellaneous)

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