Small peptide Apelin and its cognate receptor APJ, are known to play a role in tumor angiogenesis and overall cancer progession. Certain authors suggest that the Apelin receptor is also a factor in cancer immunotherapy. In this article, our goal was to study the effects of in vitro targeting of the Apelin/APJ system on the tumor cells functional properties. Protein surface and mRNA expression of Apelin and APJ had been largely examined in various tumor-derived cell lines. In contrast to the tumor tissue, the results of this study demonstrated that most tumor cell lines exhibited somewhat moderate expression of Apelin/APJ. Similar effects of APJ stimulation and inhibition had been observed in in vitro functional assays, which was due to their unusually low expression levels. Low APJ expression in cell lines has been overcome by stable APJ overexpression. In such conditions, stimulation of apelinergic system APJ-overexpressed cells affected cell functional properties in comparison to the wildtype cell lines, where overexpression of APJ receptor resulted in increased migration. On the other hand, no effect on cell proliferation was observed. Consequently, Apelin/APJ signaling in tumor-derived cell lines is not expected to play a direct and crucial role in in vitro cancer survival. Further investigation should focus on in vivo role of the apelinergic system, as demonstrated in the recently published studies, where apelinergic system is claimed to be a promising target for anti-cancer therapy.