Yaghjyan Lusine, Heng Yujing J, Sardella Brian R, Murthy Divya, Mahoney Matt B, Rosner Bernard, Polyak Kornelia, Ratcliff Maisey, Tamimi Rulla M
Department of Epidemiology, College of Public Health and Health Professions and College of Medicine, University of Florida, 2004 Mowry Rd., Gainesville, FL, 32610, USA.
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Breast Cancer Res. 2025 Apr 7;27(1):53. doi: 10.1186/s13058-025-02002-z.
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.
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.
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).
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.
胰岛素样生长因子（IGF）通路与组织重塑的自然过程有关，在此过程中细胞获得干细胞样特征。我们研究了循环中的IGF-1和IGF结合蛋白-3（IGFBP-3）与良性乳腺活检中CD44、CD24和ALDH1A1干细胞标志物表达之间的关联。
本研究纳入了护士健康研究II中151名无癌症且经活检确诊为良性乳腺疾病的女性及其血液样本。生殖和其他乳腺癌风险因素的数据通过两年一次的问卷调查获得。在组织微阵列上进行免疫组织化学（IHC）检测。对于每个核心，使用QuPath评估IHC表达，并表示为特定标志物阳性染色细胞占总细胞计数的百分比。采用广义线性回归分析血浆IGF-I和IGFBP-3（连续对数转换值和四分位数）与每个标志物（上皮和基质中）对数转换表达之间的关联，并对乳腺癌风险因素进行校正。
在多变量分析中，循环中的IGF-1和IGFBP-3连续测量值与上皮或基质中任何标志物的连续表达均无关联。IGFBP-3水平处于最高四分位数的女性，其基质CD24的表达似乎低于最低四分位数的女性（β = -0.38，95%CI -0.69，-0.08，p趋势 = 0.06）。
良性乳腺组织中循环IGFBP-3水平较高与基质CD24表达较低有关。我们的研究结果间接证明了IGF通路对乳腺上皮-间质转化和干细胞活性的诱导作用。
