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.
Highlights
The initial clinical experience from targeted therapy for breast cancer has been mixed
We have compared the expression and distribution of three widely used markers for cancer-associated fibroblasts (CAFs) and myofibroblasts—a-smooth muscle actin (ASMA), platelet-derived growth factor receptor-a (PDGFRa), and fibroblast-specific protein-1 (FSP1)—in tumours from MMTV-PyMT mice of different ages and human breast cancers
Immunostaining for ASMA, PDGFRa, and FSP1 revealed that each of the CAF markers is expressed by spindle-shaped stromal cells infiltrating into the mass of epithelial cells already at this early stage of tumour development (Figure 1A–C)
Summary
The initial clinical experience from targeted therapy for breast cancer has been mixed. 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. 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. There is a growing need for comparative studies between human and mouse tumours in order to validate preclinical models as surrogates for explorative studies aimed at finding new biomarkers and/or targets for cancer therapy
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