Anticancer efficacy of tannic acid is dependent on the stiffness of the underlying matrix

Tannic acid (TA) has been previously shown to have anticancer potential for breast cancer but its effects on melanoma have not yet been investigated. Similarly, stiffness of the tumor microenvironment is known to have a profound effect on breast cancer metastasis, but little is known about its role on melanoma. The goal of the current study is to investigate the synergistic effects of TA and matrix stiffness on melanoma progression. A375 melanoma cells with metastatic potential were cultured on TA crosslinked uncompacted (UC; soft) and electrochemically compacted (ECC; stiff) collagen gels and the effects of TA on gel morphology, mechanical properties, and cellular response (i.e. morphology and proliferation) were evaluated. SEM results showed that TA crosslinking induced merging of collagen fibrils that resulted in decrease in pore size of both UC and ECC collagen gels. Tensile testing showed that TA crosslinking significantly (p < 0.05) improved the mechanical properties of ECC collagen gels. Results from Alamar blue assay showed that TA preferentially inhibited the proliferation of A375 melanoma cells compared to the non-cancerous NIH 3T3 fibroblasts on UC collagen gels. However, on ECC collagen gels, preferential effect of TA was not prevalent as proliferation of both cell types was inhibited to a similar extent. When comparing the two gel types, inhibition of A375 melanoma cell proliferation was more pronounced on TA crosslinked UC collagen gels compared to TA crosslinked ECC collagen gels. Overall, these results suggest that TA incorporated into UC collagen gels may more selectively inhibit the proliferation of melanoma cells, and that matrix stiffness is an important driver of tumor proliferation and progression.