Document Type

Article

Publication Date

9-1-2022

Publication Title

Disease models & mechanisms

Keywords

JGM, JMG, Cancer, Genetic diversity, Mouse models, Xenograft

JAX Source

Dis Model Mech . 2022 Sep 1;15(9):dmm049457.

Volume

15

Issue

9

PMID

36037073

DOI

10.1242/dmm.049457

Grant

This study was financially supported by The Jackson Laboratory Scientific Services Innovation Fund (19005-19-05), the National Cancer Institute (R33 CA247669 to M.G.H. and M.V.W.), The Jackson Laboratory Cancer Center (P30CA034196), and the Linda Tallen and David Kane Educational Fund. X.Y.W., T.S. and J.H.C. are supported by the PDXNet Data Commons and Coordination Center funded by the National Cancer Institute (U24-CA224067 and U24-CA224067-S1). Open Access funding provided by The Jackson Laboratory.

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.

Comments

This is an Open Access article distributed under the terms of the Creative Commons Attribution

License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use,

distribution and reproduction in any medium provided that the original work is properly attributed.

Download

Share

COinS