The Expression and Function of Organic Anion Transporting Polypeptides in Normal Tissues and in Cancer

Abstract

Organic anion transporting polypeptides (OATPs) are members of the SLCO gene superfamily of proteins. The 11 human OATPs are classified in 6 families and subfamilies on the basis of their amino acid sequence similarities. OATPs are expressed in several epithelial tissues throughout the body and transport mainly amphipathic molecules with molecular weights of more than 300 kDa. Members of the OATP1 and OATP2 families are functionally the best-characterized OATPs. Among these are the multispecific OATP1A2, OATP1B1, OATP1B3, and OATP2B1. They transport various endo- and xenobiotics, including hormones and their conjugates as well as numerous drugs such as several anticancer agents. Recent reports demonstrate that some OATPs are up- or downregulated in several cancers and that OATP expression might affect cancer development. On the basis of the findings summarized in this review, we propose that OATPs could be valuable targets for anticancer therapy.

The Kidney Vero-E6 Cell Line: A Suitable Model to Study the Toxicity of Microcystins

“…They are responsible for the sodiumindependent uptake of large amphipathic endogenous and exogenous organic anions into cells and across the blood-brain barrier [9,10]. The knowledge on the mechanism(s) of OATPmediated transport is still scarce [9] however, the available information suggests that, in a general way, OATPs act as organic anion exchangers [11], functioning in a rocker-switch type of mechanism and translocating the substrate through a central positively charged pore [9].…”

“…The knowledge on the mechanism(s) of OATPmediated transport is still scarce [9] however, the available information suggests that, in a general way, OATPs act as organic anion exchangers [11], functioning in a rocker-switch type of mechanism and translocating the substrate through a central positively charged pore [9]. Some OATPs are expressed ubiquitously, whereas others are expressed in a tissue-specific way [10]. In fact, the organotropism of MC is due to the selective uptake of microcystins by the OATPs that are primarily expressed in liver [8], such as those mentioned above.…”

“…For this reason, the study of the toxicological properties of microcystins has been conducted mainly in liver cells in vivo and cultured hepatic cells in vitro. However, OATP expression in other organs has also been reported, like the case of OATP1A2 in the kidneys [7,8,10,12] and an increasing number of studies have been showing that MCLR can indeed induce nephrotox- Figure 1. Representation of the effects of microcystins in cytoskeleton, namely the changes of the hepatocytes and sinusoidal capillary structure, and intrahepatic bleeding, mediated by the inhibition of protein phosphatases PP1 and PP2A (partially adapted from [5] and [6]).…”

Regorafenib Is Transported by the Organic Anion Transporter 1B1 and the Multidrug Resistance Protein 2

“…OATPs are capable of transporting multiple compounds that affect cancer cell growth and survival, including hormones, hormone precursors, and anticancer drugs. 6) Some tyrosine kinase inhibitors are substrates or inhibitors of drug transporters. It was recently reported that nilotinib and vandetanib were transported by OATP1B1 and OATP1B3.…”

Cyanobacterial Toxins of the Laurentian Great Lakes, their Toxicological Effects, and Numerical Limits in Drinking Water

“…For example, OATPs 3A1 and 4A1 have been implicated in the uptake of MCs and these OATPs are distributed ubiquitously in human tissues [196,197].…”