The Influence of the Normal Mammary Microenvironment on Breast Cancer Cells

Abstract

The tumor microenvironment is recognized as performing a critical role in tumor initiation, progression, and metastasis of many cancers, including breast cancer. The breast cancer microenvironment is a complex mixture of cells consisting of tumor cells, immune cells, fibroblasts, and vascular cells, as well as noncellular components, such as extracellular matrix and soluble products. The interactions between the tumor cells and the tumor microenvironment modulate tumor behavior and affect the responses of cancer patients to therapies. The interactions between tumor cells and the surrounding environment can include direct cell-to-cell contact or through intercellular signals over short and long distances. The intricate functions of the tumor microenvironment in breast cancer have led to increased research into the tumor microenvironment as a possible therapeutic target of breast cancer. Though expanded research has shown the clear importance of the tumor microenvironment, there is little focus on how normal mammary epithelial cells can affect breast cancer cells. Previous studies have shown the normal breast microenvironment can manipulate non-mammary stem cells and tumor-derived cancer stem cells to participate in normal mammary gland development. The tumorigenic cells lose their tumor-forming capacity and are "redirected" to divide into "normal", non-tumorigenic cells. This cellular behavior is "cancer cell redirection". This review will summarize the current literature on cancer cell redirection and the normal mammary microenvironment's influence on breast cancer cells.

Keywords: breast cancer; microenvironment; redirection; stem cells.

Figure 1

Outline of how multiple studies have demonstrated that the normal mammary microenvironment can redirect non-mammary stem cells when placed in the in vivo mouse model of regeneration to participate in normal mammary gland regeneration [3,23,24,25,26,27].

Figure 2

Outline of how multiple studies have demonstrated that the normal mammary microenvironment can redirect cancer cells when placed in the in vivo mouse model of regeneration to participate in normal mammary gland regeneration [15,16,30,31]. TC—Testicular Carcinoma, TNBC—Triple-Negative Breast Cancer.

Figure 3

Mammary epithelial cells induce gene expression changes.