Facilitation of Breast Cancer Cell Engraftment by Human Mesenchymal Stromal Cells in Model of Experimental Metastasis

Increasing body of evidence has confirmed stromal infuence on cancer stem cells (1-3). In our work we focused on evaluation of the effect of human mesenchymal stromal cells (MSC) on breast cancer cells (BCC) in direct adherent cocultures and 3D models in vitro. We examined also the role of the MSC on BCC engraftment in experimental metastatic model in vivo. In direct cocultures we detected cell fusions, but these cells were not able to propagate. Direct cell cocultures were evaluated by flow cytometry, viability assays and kinetic assays to determine the alterations provoked in BCC by the MSC (4). Importantly, MSC and BCC coinjection resulted in higher engraftment of the BCC in mouse lungs as detected by both immunohistochemistry and PCR. Moreover, we have established the protocol for the immunomagnetic separation of the circulating tumor cells (CTC) from the breast cancer patients and evaluated the capability of these cells to initiate xenograft growth and metastatic capabilities in vivo on SCID mouse model. Based on the models with the BCC, we have coinjected the CTC and MSC to examine whether the MSC facilitated engraftment of patient-derived CTC in vivo. The data and outcomes from these experiments will be presented. Taken together we intend to exploit the established models for further exploration of the critical signals, which facilitate engraftment of the metastasis initiating cells.

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2. Kucerova L, Zmajkovic J, Toro L, Skolekova S, Demkova L, Matuskova M. Cancer Microenviron. 2015 Apr;8(1):1-14.
3. Kucerova L, Skolekova S. Neoplasma. 2013;60(1):1-10.
4. Kucerova L, Skolekova S, Matuskova M, Bohac M, Kozovska Z. BMC Cancer. 2013 Nov 9;13:535. doi: 10.1186/1471-2407-13-535.