Decreased zinc and downregulation of ZIP3 zinc uptake transporter in the development of pancreatic adenocarcinoma

Costello, Leslie C.; Levy, Bernard A.; Desouki, Mohamed Mokhtar; Zou, Jing; Bagasra, Omar; Johnson, Leslie A.; Hanna, Nader; Franklin, Renty B.

doi:10.4161/cbt.12.4.16356

Cited by 57 publications

(73 citation statements)

References 33 publications

(38 reference statements)

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“…The results showed that in most of the paired tissues, the expression levels of all the other ZIP family members except ZIP4 [11] are significantly lower in tumors than that in the surrounding benign tissues, especially those that have high endogenous expression levels (ZIP5, ZIP8 and ZIP14). Similar results were also report for ZIP3 in pancreatic adenocarcinoma tissues [27]. As for the ZnT family members, only ZnT10 showed increased expression in tumors than that in benign tissues; all the other 9 ZnT members were down-regulated in tumors.…”

Section: Discussionsupporting

confidence: 77%

Gene Profile Identifies Zinc Transporters Differentially Expressed in Normal Human Organs and Human Pancreatic Cancer

Yang¹,

Zhang²,

Cui³

et al. 2013

CMM

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Deregulated expression of zinc transporters was linked to several cancers. However, the detailed expression profile of all human zinc transporters in normal human organs and in human cancer, especially in pancreatic cancer is not available. The objectives of this study are to investigate the complete expression patterns of 14 ZIP and 10 ZnT transporters in a large number of normal human organs and in human pancreatic cancer tissues and cell lines. We examined the expression patterns of ZIP and ZnT transporters in 22 different human organs and tissues, 11 pairs of clinical human pancreatic cancer specimens and surrounding normal/benign tissues, as well as 10 established human pancreatic cancer cell lines plus normal human pancreatic ductal epithelium (HPDE) cells, using real time RT-PCR and immunohistochemistry. The results indicate that human zinc transporters have tissue specific expression patterns, and may play different roles in different organs or tissues. Almost all the ZIPs except for ZIP4, and most ZnTs were downregulated in human pancreatic cancer tissues compared to the surrounding benign tissues. The expression patterns of individual ZIPs and ZnTs are similar among different pancreatic cancer lines. Those results and our previous studies suggest that ZIP4 is the only zinc transporter that is Conflict of Interest:We declare no financial conflict of interest. significantly up-regulated in human pancreatic cancer and might be the major zinc transporter that plays an important role in pancreatic cancer growth. ZIP4 might serve as a novel molecular target for pancreatic cancer diagnosis and therapy. NIH Public Access

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Section: Discussionsupporting

confidence: 77%

Gene Profile Identifies Zinc Transporters Differentially Expressed in Normal Human Organs and Human Pancreatic Cancer

Yang¹,

Zhang²,

Cui³

et al. 2013

CMM

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“…In a current study, Costello et al found a major loss of zinc in ductal and acinar epithelium in adenocarcinoma compared to the normal epithelium (Costello et al, 2011). The decrease in zinc quantity is a characteristic not only for pancreatic cancer, but also for precursor lesions.…”

Section: Zip3 (Zinc/iron Regulated Transporter-related Protein 3) a Pmentioning

confidence: 97%

Novel Biomarkers in Pancreatic Cancer

Dima¹,

Tănase²,

Albulescu³

et al. 2012

Pancreatic Cancer - Clinical Management

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“…Potential applications for PET imaging of zinc dynamics in a broad spectrum of diseases (1)(2)(3)(4)(5)(6)(7)(8)(9)(10) motivates the development of a practical method for producing 63 Zn. Of the 3 known positronemitting zinc isotopes, 63 Zn has the most favorable properties for quantitative PET imaging in humans (Table 1), although its 38.5-m half-life will limit investigations to under 2-3 h. Nevertheless, this time frame is sufficient to determine initial biodistribution patterns of zinc after intravenous injection and evaluation of fast to moderate tissue turnover times.…”

Section: Discussionmentioning

confidence: 99%

Preparation and Preliminary Evaluation of ⁶³Zn-Zinc Citrate as a Novel PET Imaging Biomarker for Zinc

et al. 2014

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Abnormalities of zinc homeostasis are indicated in many human diseases. A noninvasive imaging method for monitoring zinc in the body would be useful to understand zinc dynamics in health and disease. To provide a PET imaging agent for zinc, we have investigated production of 63 Zn (half-life, 38.5 min) via the 63 Cu(p,n) 63 Zn reaction using isotopically enriched solutions of 63 Cu-copper nitrate. A solution target was used for rapid isolation of the 63 Zn radioisotope from the parent 63 Cu ions. Initial biologic evaluation was performed by biodistribution and PET imaging in normal mice. Methods: To produce 63 Zn, solutions of 63 Cu-copper nitrate in dilute nitric acid were irradiated by 14-MeV protons in a low-energy cyclotron. An automated module was used to purify 63 Zn from 63 Cu in the target solution. The 63 Cu-63 Zn mixture was trapped on a cation-exchange resin and rinsed with water, and the 63 Zn was eluted using 0.05 N HCl in 90% acetone. The resulting solution was neutralized with NaHCO 3 , and the 63 Zn was then trapped on a carboxymethyl cartridge, washed with water, and eluted with isotonic 4% sodium citrate. Standard quality control tests were performed on the product according to current good manufacturing practice, including radionuclidic identity and purity, and measurement of nonradioactive Zn 12 , Cu 12 , Fe 13 , and Ni 12 by ion-chromatography high-performance liquid chromatography. Biodistribution and PET imaging studies were performed in B6.SJL mice after intravenous administration of 63 Zn-zinc citrate. 63 Cu target material was recycled by eluting the initial resin with 4N HNO 3 . Results: Yields of 1.07 ± 0.22 GBq (uncorrected at 30-36 min after end of bombardment) of 63 Zn-zinc citrate were obtained with a 1.23 M 63 Cu-copper nitrate solution. Radionuclidic purity was greater than 99.9%, with copper content lower than 3 μg/batch. Specific activities were 41.2 ± 18.1 MBq/μg (uncorrected) for the 63 Zn product. PET and biodistribution studies in mice at 60 min showed expected high uptake in the pancreas (standard uptake value, 8.8 ± 3.2), liver (6.0 ± 1.9), upper intestine (4.7 ± 2.1), and kidney (4.2 ± 1.3). Conclusion: A practical and current good manufacturing practice-compliant preparation of radionuclidically pure 63 Zn-zinc citrate has been developed that will enable PET imaging studies in animal and human studies. 63 Zn-zinc citrate showed the expected biodistribution in mice.

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Decreased zinc and downregulation of ZIP3 zinc uptake transporter in the development of pancreatic adenocarcinoma

Cited by 57 publications

References 33 publications

Gene Profile Identifies Zinc Transporters Differentially Expressed in Normal Human Organs and Human Pancreatic Cancer

Gene Profile Identifies Zinc Transporters Differentially Expressed in Normal Human Organs and Human Pancreatic Cancer

Novel Biomarkers in Pancreatic Cancer

Preparation and Preliminary Evaluation of ⁶³Zn-Zinc Citrate as a Novel PET Imaging Biomarker for Zinc

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Decreased zinc and downregulation of ZIP3 zinc uptake transporter in the development of pancreatic adenocarcinoma

Cited by 57 publications

References 33 publications

Gene Profile Identifies Zinc Transporters Differentially Expressed in Normal Human Organs and Human Pancreatic Cancer

Gene Profile Identifies Zinc Transporters Differentially Expressed in Normal Human Organs and Human Pancreatic Cancer

Novel Biomarkers in Pancreatic Cancer

Preparation and Preliminary Evaluation of 63Zn-Zinc Citrate as a Novel PET Imaging Biomarker for Zinc

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Preparation and Preliminary Evaluation of ⁶³Zn-Zinc Citrate as a Novel PET Imaging Biomarker for Zinc