Cancer is one of the leading causes of death worldwide with at least 60% deaths due to metastases. The metastatic process is a complex cascade with a limiting rate of success that could be explained by the “Seed and Soil” hypothesis stating that some organs have a more suitable microenvironment for the development of metastases than others. Interestingly, the heart is an extremely rare site for metastases.

We aim at assessing the impact of the coronary effluent from contracting hearts (CH) on the last step of the metastatic cascade (colonization) by looking at the proliferation, cell cycle and death of lung metastatic cells (A549).

In order to cultivate A549 cells with conditioned medium from contracting or non-contracting hearts (NCH), an ex vivoheart contraction system (Langendorff) has been used to measure the hemodynamic parameters of hearts perfused with culture medium. Second, A549 cells have been exposed 24h to conditioned medium (10-min collection after heart stabilization) from NCH (n=15) and CH (n=15). Then, proliferation was assessed using EdU labelling and microscopy; cell cycle and cell death were assessed by cytometry.

Medium from CH decreases by 22% (P<0.01) A549 lung metastatic cells proliferation compared to medium from NCH. Moreover, we observed that A459 cells exposed to the medium from CH accumulate in G1 (+13%, P<0.05). This is associated with a 39% decrease (p=0.06) of the proportion of cells in S phase and a 43% decrease (P<0.001) in G2/M phases compared to the cells exposed to medium from NCH. However, medium from CH has no effect on cell death.

Interestingly, only medium from contracting hearts decreases cell proliferation of lung metastatic cells and makes them accumulate in G1 phase. Further studies aim at investigating the effect of the coronary effluent from CH on extravasation (belonging also to the metastatic process) and, studying the impact of medium from CH on non-metastatic cells. Then, mass spectrometry and biochemical validations will be performed in order to highlight key molecules involved in heart contraction-induced protection against metastases. To conclude, the contracting heart seems to be protected from metastases by its inhospitable microenvironment.