Zinc Suppresses Development of Pancreatic Cancer

A recent report has linked low levels of intracellular zinc and the down regulation of a gene that encodes a zinc transport protein to the development and spread of pancreatic cancer.

Investigators at the University of Maryland (Baltimore, USA) based their study of pancreatic cancer on earlier findings that had implicated zinc changes in some types of cancer.

They reported in the August 15, 2011, issue of the journal Cancer Biology & Therapy that staining of normal pancreas and adenocarcinoma tissue sections revealed a consistent major loss of zinc in ductal and acinar epithelium in adenocarcinoma compared to the normal epithelium. This decrease in zinc was evident in well differentiated through poorly differentiated stages of malignant pancreatic cancer.

Immunohistochemistry identified ZIP3 (solute carrier family 3 (zinc transporter), member 3), as the basilar membrane zinc uptake transporter in normal ductal/acinar epithelium; and that this transporter was absent in adenocarcinoma. In situ rt-PCR (real-time PCR) revealed that ZIP3 gene expression was silenced in adenocarcinoma. Treatment of malignant Panc1 cells with zinc was cytotoxic, and the combination of concurrent zinc and ZIP3 changes represented early events in the development of adenocarcinoma and suggested that zinc might be a tumor suppressor of pancreatic cancer.

“The report establishes for the first time, with direct measurements in human pancreatic tissue, that the level of zinc is markedly lower in pancreatic adenocarcinoma cells as compared with normal pancreas cells,” said first author Dr. Leslie Costello, professor of oncology and diagnostic sciences at the University of Maryland. “The fundamental implication is that we now know something about the development of pancreatic cancer that was not previously known. It provides a potential approach to treatment, that is, to find a way to get zinc back into the malignant cells, which will kill them.”

“The fact that we see the loss of the zinc transporter and a decrease in zinc in the early stages of the cancer indicates that those changes occur even before the cancer is evident. The genetic changes and the changes in zinc levels occur before the pathologist will see any changes in cells under the microscope. That is the kind of early biomarker that people need for cancers,” said Dr. Costello.

Related Links:
University of Maryland