肿瘤的异质性影响诊断、预后和治疗反应。正常和肿瘤乳腺中都存在异质性。确实，卵泡腺体内雌激素受体阴性细胞可能产生各种表型，包括雌激素受体阴性和雌激素受体阳性乳腺肿瘤。因此，肿瘤表型不一定反映癌症的起源细胞。关于雌激素受体状态，异质性可能会挑战内分泌治疗，通过消除响应性克隆，可能会导致治疗效果降低和肿瘤回归，因为耐药克隆的扩张。本研究旨在调查乳腺肿瘤的异质性及其在内分泌耐药发生中的作用。为此，我们使用了雌激素受体阳性细胞（T47D、CAMA1）和三阴性乳腺癌细胞系（TNBC；MDA-MB-231、HCC70），并采用2D和3D模型进行共培养。我们的结果表明，当雌激素受体阳性细胞与TNBC细胞共同培养时，雌激素受体状态被调节，导致对内分泌治疗的不同反应，表明不同乳腺癌细胞类型对彼此的影响会影响治疗反应。另外，在接触TNBC共培养后，雌激素受体阳性细胞的倍增时间也受到修改。进一步的实验需要完全阐明这些观察结果的分子机制。© 2023年。作者（们）在Springer Nature America，Inc.的独家许可下发表。

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.© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.