文章：

乳腺癌肿瘤中雌激素受体状态异质性：其在内分泌治疗反应中的作用

Estrogen receptor status heterogeneity in breast cancer tumor: role in response to endocrine treatment 

原文发布日期：2023-04-21 

英文摘要：

Tumor heterogeneity affects diagnosis, prognosis and response to therapy. Heterogeneity is found in both normal and neoplastic human mammary gland. Indeed, luminal ER-negative cells can give rise to various phenotypes, including ER-negative and ER-positive mammary tumors. As a result, the tumor phenotype does not necessarily reflects the cell of origin of cancer. With regard to the ER status, heterogeneity can challenge endocrine therapies, where the elimination of responsive clones could lead to reduced treatment efficacy and tumor relapse through the expansion of the resistant clones. The aim of this study was to investigate breast tumor heterogeneity and its role in endocrine resistance onset. For this purpose, we used ER+ (T47D, CAMA1) and triple-negative breast cancer cell lines (TNBC; MDA-MB-231, HCC70), co-cultures using 2D and 3D models. Our results showed that ER status is modulated when ER+ cells are cultured in the presence of TNBC cells, leading to a different response to endocrine therapy, demonstrating that the response to treatment can be affected by the influence that different breast cancer cell types exert on each other. In addition, ER+ positive cells doubling time was modified after exposure to TNBC cell co-culturing. Further experiments are required to fully elucidate the molecular mechanism of these observations. 

摘要翻译： 

肿瘤异质性影响诊断、预后及治疗反应。这种异质性存在于正常和肿瘤性人类乳腺组织中。实际上，管腔ER阴性细胞可产生多种表型，包括ER阴性和ER阳性乳腺肿瘤。因此，肿瘤表型未必反映癌症的起源细胞。就ER状态而言，异质性可能对内分泌治疗构成挑战——反应性克隆的消除可能导致治疗疗效降低，并通过耐药克隆的扩增引发肿瘤复发。本研究旨在探讨乳腺肿瘤异质性及其在内分泌抵抗发生中的作用。为此，我们采用ER阳性（T47D、CAMA1）和三阴性乳腺癌细胞系（TNBC；MDA-MB-231、HCC70），通过二维和三维模型进行共培养。结果显示当ER阳性细胞与TNBC细胞共培养时，其ER状态会发生改变，导致对内分泌治疗的反应差异，这表明不同乳腺癌细胞类型间的相互影响会改变治疗反应。此外，ER阳性细胞在与TNBC细胞共培养后倍增时间发生改变。仍需进一步实验以全面阐明这些现象背后的分子机制。

原文链接：

Estrogen receptor status heterogeneity in breast cancer tumor: role in response to endocrine treatment