Localization of the ABCG2 mitoxantrone resistance-associated protein in normal tissues

Fetsch, Patricia; Abati, Andrea; Litman, Thomas; Morisaki, Kuniaki; Honjo, Yasuko; Mittal, Khush; Bates, Susan E.

doi:10.1016/j.canlet.2005.04.024

Cited by 168 publications

(127 citation statements)

References 28 publications

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“…It is expressed in the placenta, forming part of the maternal/fetal barrier, and it contributes to the germ cell -blood barrier by its expression in the testes and the ovary (42). In the brain, ABCG2 has been detected in capillary endothelial cells in humans as well as in other species.…”

Section: Ccr Focusmentioning

confidence: 99%

The Blood-Brain Barrier and Cancer: Transporters, Treatment, and Trojan Horses

Deeken

Löscher

2007

Clinical Cancer Research

603

492

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Despite scientific advances in understanding the causes and treatment of human malignancy, a persistent challenge facing basic and clinical investigators is how to adequately treat primary and metastatic brain tumors.The blood-brain barrier is a physiologic obstruction to the delivery of systemic chemotherapy to the brain parenchyma and central nervous system (CNS). A number of physiologic properties make the endothelium in the CNS distinct from the vasculature found in the periphery. Recent evidence has shown that a critical aspect of this barrier is composed of xenobiotic transporters which extrude substrates from the brain into the cerebrospinal fluid and systemic circulation. These transporters also extrude drugs and toxins if they gain entry into the cytoplasm of brain endothelial cells before they enter the brain. This review highlights the properties of the blood-brain barrier, including the location, function, and relative importance of the drug transporters that maintain this barrier. Primary and metastatic brain malignancy can compromise this barrier, allowing some access of chemotherapy treatment to reach the tumor.The responsiveness of brain tumors to systemic treatment found in past clinical research is discussed, as are possible explanations as to why CNS tumors are nonetheless able to evade therapy. Finally, strategies to overcome this barrier and better deliver chemotherapy into CNS tumors are presented.Despite the dramatic advances in understanding the molecular basis for carcinogenesis and the development of new targeting agents to treat malignancies, a critical challenge that continues to face cancer researchers is overcoming the sanctuary for primary and metastatic disease found within the central nervous system (CNS). Brain metastases occur in a significant percentage of patients with common malignancies, with 5-year cumulative incidence rates of 16% in lung cancer patients, 7% of breast cancer patients, and 5% of patients with colon cancer (1). In diseases such as melanoma, the incidence of brain metastatic disease is reported to be as high as 55% (2). Autopsy studies show that in patients who die from cancer, up to 25% of them develop brain metastases (3).The incidence of brain metastatic disease is on the rise (4). This could be due to a number of factors, including earlier brain screening for CNS disease in cancers known to spread to the brain; improved and more widely available radiological techniques such as magnetic resonance imaging; and improved therapies to treat systemic disease, which are prolonging survival and, in turn, increasing the risk of developing metastases to the brain. The irony is that as our therapies are improving clinical outcomes and prolonging survival, the incidence of CNS disease is on the rise. Furthermore, primary brain malignancies are intrinsically resistant to most chemotherapies for reasons that are poorly understood. These realities demand that we better understand, and learn how to treat, CNS malignancy.This CNS sanctuary for metastatic as well...

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Section: Ccr Focusmentioning

confidence: 99%

The Blood-Brain Barrier and Cancer: Transporters, Treatment, and Trojan Horses

Deeken

Löscher

2007

Clinical Cancer Research

603

492

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“…ABCG2 is a half-transporter, like all members of the ABCG subfamily, and must at least dimerize to become functional. It is expressed at the apical membrane of intestinal epithelial cells (Gutmann et al, 2005), hepatocytes (Hilgendorf et al, 2007), renal tubular epithelial cells (Huls et al, 2008), endothelial vascular cells of the blood-brain and blood-testis barriers (Cooray et al, 2002;Fetsch et al, 2006), and cells of the placenta and mammary gland (Allikmets et al, 1998;Robey et al, 2011). Its expression pattern, at critical sites of uptake and elimination, resembles that of ABCB1.…”

Section: Abcg2mentioning

confidence: 99%

The Role of Canalicular ABC Transporters in Cholestasis

et al. 2014

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Cholestasis, a hallmark feature of hepatobiliary disease, is characterized by the retention of biliary constituents. Some of these constituents, such as bile acids, inflict damage to hepatocytes and bile duct cells. This damage may lead to inflammation, fibrosis, cirrhosis, and eventually carcinogenesis, sequelae that aggravate the underlying disease and deteriorate clinical outcome. Canalicular ATP-binding cassette (ABC) transporters, which mediate the excretion of individual bile constituents, play a key role in bile formation and cholestasis. The study of these transporters and their regulatory nuclear receptors has revolutionized our understanding of cholestatic disease. This knowledge has served as a template to develop novel treatment strategies, some of which are currently already undergoing phase III clinical trials. In this review we aim to provide an overview of the structure, function, and regulation of canalicular ABC transporters. In addition, we will focus on the role of these transporters in the pathogenesis and treatment of cholestatic bile duct and liver diseases.

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“…The precise physiological function of these transporters in progenitor and differentiated cells is unknown and it has been postulated that they confer protection against a number of xenobiotics, thus maintaining the regenerative capacity of the tissue (Leslie, E.M, 2005). The identification and isolation of ABCG2 positive cells in pancreatic tissue may be a new potential source of adult multipotential stem/progenitor cells, useful for the production of islet tissue for transplantation into diabetic subjects (Fetsch, PA, 2006). The presence of these cells in pancreas tissue is controversial.…”

Section: Hematoipoietic Stem Cells As a Progenitor Cells In Pancreasmentioning

confidence: 99%