Metastasis is the stage at which the prognosis substantially decreases for many types of cancer. The ability of tumor cells to metastasize is dependent upon the characteristics of the tumor cells, and the conditioning of distant tissues that support colonization by metastatic cells. In this report, we investigated the systemic alterations in distant tissues caused by multiple human breast cancer cell lines and the impact of these alterations on the tumor cell phenotype. We observed that the niche within the lung, a common metastatic site, was significantly altered by MDA-MB-231, MCF7, and T47 tumors, and that the lung microenvironment stimulated, to differing extents, an epithelial-to-mesenchymal transition (EMT), reducing proliferation, increasing transendothelial migration and senescence, with no significant impact on cell death. We also investigated the ability of an implantable scaffold, which supports the formation of a distant tissue, to serve as a surrogate for the lung to identify systemic alterations. The scaffolds are conditioned by the primary tumor similarly to the lung for each tumor type, evidenced by promoting a pro-EMT profile. Collectively, we demonstrate that metastatic and non-metastatic breast cancers condition distant tissues, with distinct effects on tumor cell responses, and that a surrogate tissue can distinguish the metastatic potential of human breast cancer cell lines in an accessible site that avoids biopsy of a vital organ.
转移是多种癌症预后显著恶化的阶段。肿瘤细胞的转移能力取决于肿瘤细胞自身的特性，以及远处组织为转移细胞定植所创造的条件。本研究中，我们探讨了多种人类乳腺癌细胞系对远处组织造成的系统性改变，以及这些改变对肿瘤细胞表型的影响。我们观察到，作为常见转移部位的肺内微环境在MDA-MB-231、MCF7和T47肿瘤作用下发生显著改变，且肺微环境在不同程度上刺激了上皮-间质转化（EMT），同时抑制细胞增殖、增强跨内皮迁移能力并促进细胞衰老，但对细胞死亡无显著影响。此外，我们研究了一种可植入支架作为肺组织替代物以识别系统性改变的能力，该支架支持远处组织形成。研究显示，对于每种肿瘤类型，原发肿瘤对支架产生的条件化作用与对肺组织的作用相似，均表现为促进促EMT特征的形成。综上所述，本研究表明转移性与非转移性乳腺癌均可对远处组织产生条件化作用，并对肿瘤细胞反应产生不同影响，且替代组织可在无需对重要器官进行活检的可及部位，有效区分人类乳腺癌细胞系的转移潜能。
肿瘤(癌症)患者之家