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Apoptotic cell death in mammary adenocarcinoma cells is prevented by soluble factors present in the target organ of metastasis

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Abstract

Target organ of metastasis determines the fate of metastasis. The soluble factors released from one or more cell types in the new stroma may influence growth and survival of metastatic cells. In the present study, we used conditioned media from the kidney, liver and lung, the latter being the target organ of metastasis of murine mammary adenocarcinoma cell lines LM3, LMM3 and F3II, to assess whether the soluble factors released from these organs could modulate in vitro survival of these cell lines after apoptosis-inducing treatments and to investigate the mechanisms involved in this effect. We demonstrate that conditioned medium from lung, but not from liver or kidney, promotes survival of these cells after doxorubicin, cisplatin, agonistic anti-Fas antibody and serum withdrawal treatments. Furthermore, LMM3 cells treated with lung conditioned medium after doxorubicin exposure maintained their tumorigenic capacity and metastatic potential. Neither IGF nor EGF could promote survival but, surprisingly, TGF-β could reduce sensitivity of LMM3 cells to doxorubicin in vitro. Doxorubicin treatment induced Bax expression and down-regulated Bcl-2 expression. In contrast, lung conditioned medium increased Bcl-2 expression and inhibited doxorubicin-mediated Bcl-2 down-regulation. Neither of those treatments alone modified Bcl-xL expression, although co-treatment induced a 3- to 5-fold increase of its expression. These results suggest that the lung microenvironment could promote metastasis of these adenocarcinoma cell lines by increasing survival of metastatic cells, possibly by modulation of Bcl-2 protein family expression.

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  1. Cell Biology Department, Research Area, Institute of Oncology 'Angel H. Roffo', University of Buenos Aires, Buenos Aires, Argentina

    Virginia Ladeda, Alejandro P. Adam, Lydia Puricelli & Elisa Bal De Kier Joffé

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  1. Virginia Ladeda
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Ladeda, V., Adam, A.P., Puricelli, L. et al. Apoptotic cell death in mammary adenocarcinoma cells is prevented by soluble factors present in the target organ of metastasis. Breast Cancer Res Treat 69, 39–51 (2001). https://doi.org/10.1023/A:1012201805486

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