The obese inflammatory microenvironment may promote breast DCIS progression

Area of Science:

• Breast cancer research
• Tumor microenvironment
• Adipose tissue biology

Background:

• Ductal carcinoma in situ (DCIS) is a non-invasive breast cancer.
• Obesity and its associated inflammatory adipose microenvironment may drive DCIS progression to invasive ductal carcinoma (IDC).
• Understanding the interactions between DCIS cells, myoepithelial cells (MECs), and the adipose microenvironment is crucial.

Purpose of the Study:

• To investigate the influence of the inflammatory adipose microenvironment on DCIS progression.
• To assess interactions between DCIS cells, MECs, adipocytes, and macrophages.

Main Methods:

• Development of a 3D co-culture model using DCIS-like tumoroids, adipose cells, and macrophages.
• Comparison of tumoroid behavior in inflammatory versus non-inflammatory adipose microenvironments.
• Analysis of gene expression in tumoroids, adipocytes, and macrophages.

Main Results:

• Inflammatory conditions promoted cancer cell survival and invasion genes while inhibiting apoptosis genes.
• MECs' protective function was compromised.
• Obese adipocytes exhibited myofibroblast-associated gene expression (myoCAFs), while normal-weight adipocytes showed inflammatory fibroblast phenotypes (iCAF); both influenced macrophage polarization.

Conclusions:

• Reciprocal interactions between tumoroids and the adipose microenvironment, especially in obesity, drive breast cancer progression.
• The integrity of the MEC layer is disrupted by these interactions.
• Adipose tissue plays a significant role in breast cancer progression.