Inhibition of the Lysophosphatidylinositol Transporter ABCC1 Reduces Prostate Cancer Cell Growth and Sensitizes to Chemotherapy

Expression of ATP-binding cassette (ABC) transporters has long been implicated in cancer chemotherapy resistance. Increased expression of the ABCC subfamily transporters has been reported in prostate cancer, especially in androgen-resistant cases. ABCC transporters are known to efflux drugs but, recently, we have demonstrated that they can also have a more direct role in cancer progression. The pharmacological potential of targeting ABCC1, however, remained to be assessed. In this study, we investigated whether the blockade of ABCC1 affects prostate cancer cell proliferation using both in vitro and in vivo models. Our data demonstrate that pharmacological inhibition of ABCC1 reduced prostate cancer cell growth in vitro and potentiated the effects of Docetaxel in vitro and in mouse models of prostate cancer in vivo. Collectively, these data identify ABCC1 as a novel and promising target in prostate cancer therapy

New trends in the development of multifunctional peptides to functionalize biomaterials

Improving cell-material interactions is a major goal in tissue engineering. In thisregard, functionalization of biomaterials with cell instructive molecules from theextracellular matrix stands out as a powerful strategy to enhance their bioactivity andachieve optimal tissue integration. However, current functionalization strategies, likethe use of native full-length proteins, are associated with drawbacks, thus urging theneed of developing new methodologies. In this regard, the use of synthetic peptidesencompassing specific bioactive regions of proteins represents a promising alterna-tive. In particular, the combination of peptide sequences with complementary or syn-ergistic effects makes it possible to address more than one biological target at thebiomaterial surface. In this review, an overview of the main strategies using peptidesto install multifunctionality on biomaterials is presented, mostly focusing on the com-bination of the RGD motif with other peptides sequences. The evolution of theseapproaches, starting from simple methods, like using peptide mixtures, to moreadvanced systems of peptide presentation, with very well defined chemical proper-ties, are explained. For each system of peptide's presentation, three main aspects ofmultifunctionality—improving receptor selectivity, mimicking the extracellular matrixand preventing bacterial colonization while improving cell adhesion—are highlighted.Peer ReviewedPostprint (published version