LBPO.TB01 · 肿瘤生物学 · Late-Breaking
年轻乳腺脂肪组织中年龄依赖性的基质体重塑揭示肿瘤侵袭性的潜在机制
Age-dependent matrisome remodeling in young breast adipose tissue identifies a potential mechanism of tumor aggressiveness
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
细胞外基质（ECM）是乳腺组织稳态的动态调节因子，在乳腺癌进展中发挥关键作用。在整个生命过程中，乳腺组织经历广泛重塑，驱动 ECM 结构、沉积和基质体组成的变化。这些变化是疾病发生、临床结局和肿瘤侵袭性方面所观察到的年龄差异的基础。在年轻（<40 岁）乳腺组织中，与老年组织相比，ECM 蛋白沉积更为丰富，胶原纤维更粗且排列更整齐。老年乳腺组织的特征在体内已与侵袭性疾病相关联；然而，小鼠组织在生理学上与人类组织不同，无法完全再现肿瘤与其微环境之间的复杂相互作用。迄今为止，人类乳腺脂肪组织中年龄依赖性的 ECM 重塑仍未被充分界定，凸显了对 ECM 和乳腺衰老原代模型的需求。为满足这一需求并确定驱动侵袭性乳腺癌表型的 ECM 蛋白，我们对老年（>50 岁）和年轻（<40 岁）女性的健康乳腺脂肪组织进行了蛋白质分析，并结合 ECM 和组织结构分析。与现有发现相反，通过 Masson 三色染色和刚度流变学测量，我们观察到老年组织和年轻组织之间总胶原组成没有差异。然而，蛋白质组学分析揭示年轻女性中 I、IV、V 和 XV 型胶原表达增加，这与他人在小鼠乳腺组织中发表的现有研究一致。Periostin（POSTN）是一种创伤愈合反应和胶原合成所需的基质细胞蛋白，其表达在年轻乳腺脂肪中升高。此外，对人类肿瘤样本 RNA-Seq 的数据挖掘发现，POSTN 表达随与肿瘤组织的接近程度而增加，并在激素受体阳性癌症中富集。综上所述，这些数据表明乳腺脂肪中的 ECM 具有年龄特异性，胶原含量和 ECM 调节因子（如 POSTN）的变化可能促成年轻女性的侵袭性乳腺癌。
查看英文原文 English abstract
The extracellular matrix (ECM) is a dynamic regulator of breast tissue homeostasis and plays a critical role in breast cancer progression.Across the lifespan, breast tissue undergoes extensive remodeling that drives changes in ECM architecture, deposition, and matrisome composition. These changes underlie age-differences observed in disease development, clinical outcome, and tumor aggressiveness. In young (<40 years) breast tissue, ECM protein deposition is more abundant, and collagen fibers are thicker and more aligned compared to aged tissue. Features of aged mammary tissue have been linked to aggressive disease in vivo ; however, murine tissues are physiologically distinct from human tissue and do not fully recapitulate the complex interactions between the tumor and its microenvironment. To date, age-dependent ECM remodeling in human breast adipose tissue remains poorly defined., highlighting the need for primary models of ECM and breast aging. To address this need and to identify ECM proteins driving aggressive breast cancer phenotypes, we performed protein profiling of healthy breast adipose tissue from aged (>50) and young (<40) women, combined with analyses of ECM and tissue architecture. Contrary to existing findings, we observed no difference in total collagen composition via Masson's trichrome staining and rheological measures of stiffness between the aged and young tissues. However, proteomic analysis revealed increased expression of collagen types I, IV, V, and XV in young women, consistent with existing studies published by others in mouse mammary tissue. Periostin (POSTN) expression, a matricellular protein required for the wound healing response and collagen synthesis, was elevated in the young breast adipose. Additionally, data mining from RNA-Seq of human tumor samples uncovered that POSTN expression increases with proximity to tumor tissue and is enriched in hormone receptor positive cancers. Taken together, these data demonstrate that the ECM in the breast adipose is age-specific and that shifts in collagen content and ECM regulators, such as POSTN, may contribute to aggressive breast cancer in young women.
利益披露 Disclosure
M. Hawes, None..
K. Salim, None..
N. Cullen, None..
K. Herbert, None..
D. Carlino, None..
B. Bunnell, None..
B. Collins-Burow, None..
V. Barnes, None..
J. Belgodere, None..
M. Burow, None..
E. Martin, None.