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Updated: May 15, 2025
Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples
Published on: October 2, 2020
Associations of circulating insulin-like growth factor-1 and insulin-like growth factor binding protein-3 with the
Lusine Yaghjyan1, Yujing J Heng2, Brian R Sardella2
1Department of Epidemiology, College of Public Health and Health Professions and College of Medicine, University of Florida, 2004 Mowry Rd., Gainesville, FL, 32610, USA. lyaghjyan@ufl.edu.
Background:
The insulin-like growth factor (IGF) pathway is implicated in a naturally occurring process of tissue remodeling during which cells acquire stem cell-like characteristics. We examined associations of circulating IGF-1 and IGF binding protein-3 (IGFBP-3) with expression of CD44, CD24, and ALDH1A1 stem cell markers in benign breast biopsies.
Methods:
This study included 151 cancer-free women with incident biopsy-confirmed benign breast disease and blood samples within the Nurses' Health Study II. The data on reproductive and other BCa risk factors were obtained from biennial questionnaires. Immunohistochemistry (IHC) was done on tissue microarrays. For each core, the IHC expression was assessed using QuPath, and expressed as % of cells that stain positively for a specific marker out of the total cell count. Generalized linear regression was used to examine the associations of plasma IGF-I and IGFBP-3 (continuous log-transformed and quartiles) with log-transformed expression of each marker (in epithelium and stroma), adjusted for BCa risk factors.
Results:
In multivariate analysis, continuous circulating IGF-1 and IGFBP-3 measures were not associated with the continuous expression of any of the markers in the epithelium or stroma. Women whose IGFBP-3 levels were in the top quartile appeared to have lower expression of stromal CD24 compared to those in the lowest quartile (β = - 0.38, 95% CI - 0.69, - 0.08, p-trend = 0.06).
Conclusions:
Higher circulating IGFBP-3 levels were associated with lower stromal CD24 expression in benign breast tissue. Our findings provide indirect evidence of the inducing effect of IGF pathway on epithelial-to-mesenchymal transitions and stem cell activity in the breast.
