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原发乳腺癌组织中的间充质干细胞通过 EGF/EGFR/Akt 通路部分促进肿瘤增殖和增强类乳腺球体形成。

Mesenchymal stem cells from primary breast cancer tissue promote cancer proliferation and enhance mammosphere formation partially via EGF/EGFR/Akt pathway.

机构信息

Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, 27 Taiping Road, Beijing 100850, China.

出版信息

Breast Cancer Res Treat. 2012 Feb;132(1):153-64. doi: 10.1007/s10549-011-1577-0. Epub 2011 May 17.

Abstract

Mesenchymal stem cells (MSCs) play a critical role in promoting cancer progression. However, it is not clear whether MSCs are located in breast cancer tissues and correlated with tumor proliferation. The aim of this study was to investigate the presence of MSCs in breast cancer tissues and evaluate their interactions with cancer cells. We successfully isolated and identified MSCs from primary breast cancer tissues. Breast cancer-associated MSCs (BC-MSCs) showed homogenous immunophenotype, and possessed tri-lineage differentiation potential (osteoblast, adipocyte, and chondrocyte). When co-transplanted with cancer cells in a xenograft model in vivo, BC-MSCs significantly increased the volume and weight of tumors. We observed that BC-MSCs stimulated mammosphere formation in the transwell co-culture system in vitro. This effect was significantly suppressed by the EGF receptor inhibitor. We verified that BC-MSCs could secrete EGF and activate cancer cell's EGF receptors. Furthermore, our data showed that EGF derived from BC-MSCs could promote mammosphere formation via the PI3K/Akt signaling pathway. Our results confirmed the presence of MSC in primary breast cancer tissues, and they could provide a favorable microenvironment for tumor cell growth in vivo, partially enhance mammosphere formation via the EGF/EGFR/Akt pathway.

摘要

间充质干细胞(MSCs)在促进癌症进展中起着关键作用。然而,目前尚不清楚 MSCs 是否位于乳腺癌组织中,以及它们是否与肿瘤增殖相关。本研究旨在探讨 MSCs 是否存在于乳腺癌组织中,并评估它们与癌细胞的相互作用。我们成功地从原发性乳腺癌组织中分离和鉴定了 MSCs。乳腺癌相关 MSCs(BC-MSCs)具有均匀的免疫表型,并具有三系分化潜能(成骨细胞、脂肪细胞和成软骨细胞)。当在体内异种移植模型中与癌细胞共移植时,BC-MSCs 显著增加了肿瘤的体积和重量。我们观察到 BC-MSCs 在体外 Transwell 共培养系统中刺激类乳腺球体形成。这种作用被表皮生长因子受体抑制剂显著抑制。我们验证了 BC-MSCs 可以分泌表皮生长因子并激活癌细胞的表皮生长因子受体。此外,我们的数据表明,BC-MSCs 分泌的表皮生长因子可以通过 PI3K/Akt 信号通路促进类乳腺球体形成。我们的结果证实了 MSC 存在于原发性乳腺癌组织中,它们可以在体内为肿瘤细胞生长提供有利的微环境,部分通过表皮生长因子/表皮生长因子受体/丝氨酸-苏氨酸激酶途径增强类乳腺球体形成。

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