Enhanced expression of organic anion transporting polypeptides (OATPs) in androgen receptor-positive prostate cancer cells: Possible role of OATP1A2 in adaptive cell growth under androgen-depleted conditions

Abstract

The biological mechanisms underlying castration resistance of prostate cancer are not fully understood. In the present study, we examined the role of organic anion transporting polypeptides (OATPs) as importers of dehydroepiandrosterone sulfate (DHEAS) into cells to support growth under androgen-depleted conditions. Cell growth and mRNA expression of OATP genes were studied in human prostate cancer LNCaP and 22Rv1 cells under androgen-depleted conditions. The stimulatory effect of DHEAS on cell growth was investigated in LNCaP cells in which OATP1A2 had been silenced. Growth of both cell lines was stimulated by DHEAS and the effect was attenuated by STX64, an inhibitor of steroid sulfatase which can covert DHEAS to DHEA. OATP1A2 mRNA expression was increased most prominently among various genes tested in LNCaP cells grown in androgen-depleted medium. Similar results were obtained with 22Rv1 cells. Furthermore, the characteristics of

Role of Organic Anion-Transporting Polypeptides (OATPs) in Cancer Therapy

“…Certain (60) ↑ in prostate cancer cells (6) qRT-PCR Kidney (64) ↑ in bone cancer (65) RT-PCR OATP1B1 Liver (2,66) ↓ in liver cancer (37)(38)(39)67,68) RT-PCR, IF, IB ↑ in colon polyps and colon cancer (63) RT-PCR ↑ in ovarian cancer (69) RT-PCR OATP1B3 Liver (3,70) ↓ in liver cancer (41) qRT-PCR, IB ↑ in colon cancer (4,71,72) RT-PCR, qRT-PCR, IB, IHC ↑ in pancreatic cancer (71)(72)(73) RT-PCR, qRT-PCR, IB, IHC ↑ in lung cancer (38) RT-PCR, qRT-PCR, IF ↑ in prostate cancer (16,17,68,74) qRT-PCR, IF ↑ in breast cancer (75) qRT-PCR, IHC ↑ in testicular cancer (68) qRT-PCR, IF ↑ in ovarian cancer (69) RT-PCR OATP1C1 Brain (76) ↑ in bone cancers (65) RT-PCR Testes (76) Ciliary body (77) OATP2A1 Ubiquitous (78) ↑ in breast cancer (79) qRT-PCR ↑ in liver cancer (80) qRT-PCR, IF ↑ in bone metastases from kidney cancer (65) qRT-PCR, IB ↓ in cancers of bowel, stomach, ovary, lung, and kidney (81) RT-PCR OATP2B1 Blood-brain barrier (82) ↑ in bone cancer (65) RT-PCR Heart (83) ↑ in breast cancers (79,84) qRT-PCR, IF, IB Enterocytes (85) ↓ in liver and pancreatic cancers (68) qRT-PCR Liver (86) Placenta (87) OATP3A1 Ubiquitous (88) ↑ in bone cysts …”

“…Given that OATP1A2 can mediate the transport of endogenous hormonal substrates and several anticancer drugs (Table I), several investigations have examined the expression and functional impact of OATP1A2 in cancer. OATP1A2 expression was first reported in breast cancer and subsequently in additional types of cancer including colon, prostate, and bone (Table II) (6,(61)(62)(63)65). To date, the potential functional significance of OATP1A2 has been reported in breast cancer, but not in other types of cancer.…”

“…Arakawa et al reported that OATP1A2 is expressed in human prostate cancer cell lines (LNCaP and 22Rv1) and facilitates the uptake of DHEA-S and enhances cancer cell growth under androgen-depleted conditions (6). The levels of OATP1A2 mRNA were reported to be elevated in human osteosarcoma cell lines (HOS and MG-63) and human kidney cancer cells metastasized to bone tissue (65).…”

“…Subsequent reports revealed that the expression of OATPs may be altered in different disease conditions including cancer and may play a potential role in the development and progression of cancer as well as the disposition of anticancer drugs (2)(3)(4)(5)(6). Given that the role of OATPs in handling cancer therapeutics has been already covered by several excellent reviews (7)(8)(9)(10), this review will focus on the recent findings in the field.…”

A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer

“…54,55 These transporters are also expressed in CRPC tumors and cell lines including PC3 and LNCaP cells. [56][57][58][59] However, no transporter has been identified for nilotinib, suggesting a passive transport across the cell membrane. 25 The cellular efflux mechanisms of sorafenib and nilotinib have been reported in various studies and involved breast cancer resistance protein (BCRP), P-glycoprotein (P-gp), and multidrug resistance protein (MRP)-2 for sorafenib only.…”