Increased Expression of ABCB6 Enhances Protoporphyrin IX Accumulation and Photodynamic Effect in Human Glioma

Zhao, Shen; Chen, Xiaofeng; Wang, Ligang; Yang, Guang; Han, Dayong; Teng, Lisong; Yang, Ming; Wang, Dayong; Chen, Shi; Liu, Yao-Hua; Zheng, Bingjie; Shi, Changbin; Gao, Xu; Rainov, Nikolai G.

doi:10.1245/s10434-011-2201-6

Cited by 89 publications

(68 citation statements)

References 34 publications

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“…Therefore, ABCB6 was thought to be primarily involved in the transporting coproporphyrin III into the mitochondria for PpIX/heme b synthesis (79). Increased ABCB6 expression has been linked to an increase in fluorescence in human glioma tissues allowing for better contrast in fluorescence-guided surgery, via more sufficient PpIX accumulation (80). ABCB6 is located in the cell membrane and Golgi apparatus, and transports coproporphyrinogen III between the cellular departments (81–83).…”

Section: ‘Pro-dye’ Fluorescent Agent 5-alamentioning

confidence: 99%

Fluorescent contrast agents for tumor surgery (Review)

Xiao

Chen

2018

Exp Ther Med

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Cancer is a leading cause of cases of mortality worldwide. The most effective method to cure solid tumors is surgery. Every year, >50% of cancer patients receive surgery to remove solid tumors. Surgery may increase the cure rate of most solid tumors by 4–11 fold. Surgery has many challenges, including identifying small lesions, locating metastases and confirming complete tumor removal. Fluorescence guidance describes a new approach to improve surgical accuracy. Near-infrared fluorescence imaging allows for real-time early diagnosis and intraoperative imaging of lesion tissue. The results of previous preclinical studies in the field of near-infrared fluorescence imaging are promising. This review provides examples introducing the three kinds of fluorescent dyes: The passive fluorescent dye indocyanine green, which has been approved by the Food and Drug Administration for clinical use in the USA, the fluorescent prodrug 5-aminolevulinic acid, a porphyrin precursor in the heme synthesis, and biomarker-targeted fluorescent dyes, which allow conjugation to different target sites.

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Section: ‘Pro-dye’ Fluorescent Agent 5-alamentioning

confidence: 99%

Fluorescent contrast agents for tumor surgery (Review)

Xiao

Chen

2018

Exp Ther Med

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“…activity towards porphyrins impacts heme metabolism [29], hematopoiesis [30], photodynamic therapy [31] and parasite killing in macrophages [32]. Therefore, a heterologous expression system with correctly folded human ABCB6 expressed in a eukaryotic host with glycosylation patterns and membrane lipid composition similar to mammalian ones would greatly help the complicated task of unraveling the molecular questions of ABCB6 biochemistry.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Leishmania tarentolae as a host for heterologous expression of functional human ABCB6 transporter

Grebowski¹,

Studzian²,

Bartosz³

et al. 2016

Biochimica et Biophysica Acta (BBA) - Biomembranes

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The need for large amounts of reproducibly produced and isolated protein arises not only in structural studies, but even more so in biochemical ones, and with regard to ABC transporters it is especially pressing when faced with the prospect of enzymatic/transport activity studies, substrate screening etc. Thus, reliable heterologous expression systems/model organisms for large and complex proteins are at a premium. We have verified the applicability of the recently established novel eukaryotic expression system, using Leishmania tarentolae as a host, for human ABC protein overexpression. We succeeded in overexpressing human ABCB6, a protein with controversial subcellular localization and multiple proposed cellular functions. We were able to demonstrate its efficient expression in the expected subcellular locations as well as biochemical activity of the overexpressed protein (ATPase activity and porphyrin-like substrate transport). This activity was absent in cells overexpressing the catalytically inactive variant of ABCB6 (K629M). We demonstrate the possibility of applying a cost-effective expression system to study the activity of membrane transporters from the ABC superfamily.

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“…Glioma tissue was intraoperatively characterized by strong PpIX fluorescence, whereas normal tissue revealed no visible PpIX. A more recent study demonstrated that the accumulation of 5-ALA-mediated PpIX in glioma cells is enhanced by increased expression of the ABC mitochondrial porphyrin importer ABCB6, and that ABCB6 expression was greatly elevated in human gliomas compared with normal brain tissue (118).…”

Section: Intraoperative Imaging Of Tumors or Their Metastasesmentioning

confidence: 99%

Molecular Imaging of Membrane Transporters’ Activity in Cancer: a Picture is Worth a Thousand Tubes

Mann

Semenenko

Meir

et al. 2015

AAPS J

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Abstract. Molecular imaging allows the non-invasive assessment of membrane transporter expression and function in living subjects. Such technologies have the potential to become diagnostic and prognostic tools, allowing detection, localization, and prediction of response of tumors and their metastases to therapy. Beyond tumors, imaging can also help understand the role of transporters in adverse drug effects and drug clearance. Here, we review molecular imaging technologies that monitor transporter-mediated processes. We emphasize emerging probe substrates and potential clinical applications of imaging the function of membrane transporters in cancer.

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Increased Expression of ABCB6 Enhances Protoporphyrin IX Accumulation and Photodynamic Effect in Human Glioma

Cited by 89 publications

References 34 publications

Fluorescent contrast agents for tumor surgery (Review)

Fluorescent contrast agents for tumor surgery (Review)

Leishmania tarentolae as a host for heterologous expression of functional human ABCB6 transporter

Molecular Imaging of Membrane Transporters’ Activity in Cancer: a Picture is Worth a Thousand Tubes

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