Human Breast Cancer Cell Lines Differentially Modulate Signaling from Distant Microenvironments, Which Reflects Their Metastatic Potential

Simple Summary Metastasis is the stage at which the prognosis substantially decreases for many types of cancer. The ability of cancer cells to disseminate to distant organs, such as the lung, in the body is dependent on the conditioning of these distant sites by the primary tumor. Herein, we investigated the characteristics of the lung, a common site of metastasis, for human breast cancer cell lines that are either metastatic or non-metastatic. The characteristics of the lung were significantly altered by both metastatic and non-metastatic cancer cells, though the non-metastatic cells had distinct effects relative to the metastatic cells. We also investigated the use of a synthetic niche as a surrogate for the lung, which recapitulated the effects of the metastatic and non-metastatic cells. The analysis of the synthetic niche may provide an opportunity to identify disease aggressiveness without the risks associated with the biopsy of vital organs.Abstract 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.