Department of Medicine, University of Udine, Udine, Italy.
School of Life Sciences, University of Sussex, Brighton, UK.
Cancer Gene Ther. 2023 Jul;30(7):932-935. doi: 10.1038/s41417-023-00618-x. Epub 2023 Apr 21.
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.
肿瘤异质性影响诊断、预后和治疗反应。正常和肿瘤人类乳腺中都存在异质性。事实上，腔 ER 阴性细胞可以产生各种表型，包括 ER 阴性和 ER 阳性乳腺肿瘤。因此，肿瘤表型不一定反映癌症的起源细胞。就 ER 状态而言，异质性可能会挑战内分泌治疗，因为消除敏感克隆可能会导致治疗效果降低和肿瘤复发，原因是耐药克隆的扩增。本研究旨在研究乳腺肿瘤异质性及其在内分泌耐药发生中的作用。为此，我们使用 ER（T47D、CAMA1）和三阴性乳腺癌细胞系（TNBC；MDA-MB-231、HCC70），在 2D 和 3D 模型中进行共培养。我们的结果表明，当 ER 细胞在 TNBC 细胞存在的情况下培养时，ER 状态会发生调节，导致对内分泌治疗的反应不同，这表明治疗反应可能会受到不同乳腺癌细胞类型相互影响的影响。此外，ER 阳性细胞在暴露于 TNBC 细胞共培养后倍增时间发生改变。需要进一步的实验来充分阐明这些观察结果的分子机制。
