Of mice and men: a comparative study of cancer-associated fibroblasts in mammary carcinoma

Abstract

Introduction. The initial clinical experience from targeted therapy for breast cancer has been mixed. While important progress has been made in the care of a subset of patients characterized by amplification of HER2 through the use of trastuzumab, other targeted therapies have failed to improve the outcome for large, unselected groups of patients. Thus, efforts to find prognostic or predictive biomarkers to enable tailored therapy are highly warranted. Genetically engineered mouse models of human cancer provide a convenient setting in which to perform explorative studies. However, there is a paucity of comparative studies between mouse and human tumours in order to validate the use of mouse models as discovery tools.

Materials and methods. Here, we have compared the localization of markers for cancer-associated fibroblasts in the MMTV-PyMT mouse model of mammary carcinoma with that of human breast cancer. The expression of α-smooth muscle actin, platelet-derived growth factor receptor-α, and fibroblast-specific protein-1 was assessed by immunostaining of sections from tumours of MMTV-PyMT mice. Information about the distribution of the same markers in human breast cancer was derived from the publicly available database the Human Protein Atlas.

Results. Both mouse and human mammary carcinomas were infused by a rich fibrotic stroma. While no marker was capable of identifying all stromal fibroblasts, the expression pattern of each marker was remarkably similar in mouse and human.

Discussion. We conclude that the MMTV-PyMT mouse model of breast cancer will have utility as a discovery tool for biomarkers of cancer-associated fibroblasts during malignant conversion.

Key words::

• Biomarkers
• breast neoplasms
• fibroblast

Acknowledgements

K.P. is the recipient of a Young Investigator Award from the Swedish Cancer Society. This work was supported by grants to K.P. from the Swedish Cancer Society, the Swedish Research Council (project# K2011-67X-21865-01-6), the Swedish Childhood Cancer Society, the KI Cancer network, Jeansson's foundation, Magnus Bergvall's foundation, and Åke Wiberg's foundation. In addition, support was provided by a Linnaeus grant to the STARGET consortium from the Swedish Research Council, and by strategic funds to the BRECT network from Karolinska Institutet and Stockholm County.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.