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. 2014 Apr 1;3(2):107-14.
doi: 10.4161/adip.28250. Epub 2014 Feb 20.

Gene Expression Differences in Adipose Tissue Associated With Breast Tumorigenesis

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Free PMC article

Gene Expression Differences in Adipose Tissue Associated With Breast Tumorigenesis

Lori A Sturtz et al. Adipocyte. .
Free PMC article

Abstract

Long thought to function only as an inert energy storage depot, the role of adipose tissue in breast tumorigenesis has been largely ignored. In light of increasing rates of obesity and use of breast conserving therapy and autologous fat grafting, improved understanding of the role of adipose tissue in tumor etiology is crucial. Thus, adipose tissue adjacent to and distant from invasive breast tumors (n = 20), or adjacent to non-malignant diagnoses (n = 20) was laser microdissected from post-menopausal women. Gene expression data were generated using microarrays and data analyzed to identify significant patterns of differential expression between adipose tissue groups at the individual gene and molecular pathway level. Pathway analysis revealed significant differences in immune response between non-malignant, distant, and tumor-adjacent adipose tissue, with the highest response in tumor-adjacent and lowest in non-malignant adipose tissue. Adipose tissue from invasive breasts exhibits increased expression of anti-inflammatory genes such as MARCO and VSIG4 while genes differentially expressed between tumor-adjacent and distant adipose tissue such as SPP1, RRM2, and MMP9, are associated with increased cellular proliferation, invasion, and angiogenesis. These data suggest that molecular profiles of adipose tissue differ depending on presence of or proximity to tumor cells. Heightened immunotolerance in adipose tissue from invasive breasts provides a microenvironment favorable to tumorigenesis. In addition, tumor-adjacent adipose tissue demonstrates expression of genes associated with tumor growth and progression. Thus, adipose tissue is not an inert component of the breast microenvironment but plays an active role in tumorigenesis.

Keywords: adipose; breast cancer; gene expression; microenvironment.

Figures

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Figure 1. Relative gene expression levels of RRM2 in tumor-adjacent, distant, and non-malignant adipose tissue. Data was generated by qRT-PCR in 10 pairs of independent tumor-adjacent and distant adipose tissue samples as well as nine independent non-malignant adipose tissue samples. Median relative expression levels were 3979 in tumor-adjacent, 1428 in distant, and 307 in non-malignant adipose tissue. Blue diamonds, tumor-adjacent tissue; red triangles, distant tissue; green triangles, non-malignant tissue.
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Figure 2. H&E stained images of tumor-adjacent and distant adipose tissue from a patient with invasive breast cancer. The image on the left is adipose tissue adjacent to an ER+/PR/HER2, moderately-differentiated IDCA. The image on the right is distant adipose tissue located 4 cm from the tumor.

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