The tumorigenicity of breast cancer cells is reduced upon treatment with exosomes purified from heparin - treated cell cultures

Background: Cell surface heparan-sulfate proteoglycans (HPSGs) play a central role in controlling the genotype and phenotype of eukaryotic cells and have been implicated in a wide range of pathologies including cancer. Heparin is often used as a specific probe of the role of HPSGs in cell physiology and we have previously shown a reduction in the tumorigenicity of breast cancer cells when cultured in its presence. However, a partial reversal of the anti-tumorigenic effect occurred when the treated cells were cultured in fresh medium without heparin, which led us to consider whether a more persistent effect could be achieved by treatment of the cells with exosomes from heparin treated cells. Methods The tumorigenicity was analysed using exosomes from the culture medium of heparin treated MCF-7 and MDA-MB231 breast cancer cells (Exo-HT) or from conditioned medium following the termination of treatment (heparin discontinued, Exo-HD). Results Tumorigenicity was reduced in cells cultured in the presence of Exo-HT compared to that of cells cultured in the presence of exosomes from untreated cells (Exo-Ctrl). Exo-HD were also observed to exert an anti-tumorigenic effect in terms of the level of expression of pro - tumorigenic and cell cycle regulatory proteins as well as signalling activities when added to fresh cultures of MCF-7 and MDA-MB231 cells, an effect not seen upon treatment with Exo-Ctrl. The anti-tumorigenic activity of the heparin-derived exosomes may arise from observed changes in the miRNA content or from heparin, which was observed to be bound to the exosomes. Conclusion The anti-tumorigenic effect of heparin treatment of cancer cells was also observed upon treatment with heparin-derived exosomes.