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Environmental Factor, March 2013

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NTP postdoc wins top award at SOT

By Robin Mackar and Martha Lindauer

Yuanyuan (Laura) Xu, Ph.D.

Award-winning postdoctoral researcher Xu. (Photo courtesy of Steve McCaw)

Michael Waalkes, Ph.D.

Mentor Waalkes (Photo courtesy of Steve McCaw)

Yuanyuan (Laura) Xu, Ph.D., of the National Toxicology Program (NTP) Laboratory, will be honored with the Best Postdoctoral Publication Award as part of the Society of Toxicology (SOT) Annual Meeting March 10-14 in San Antonio. Xu, a third-year postdoctoral fellow in the NTP Inorganic Toxicology Group, led by Michael Waalkes, Ph.D., is being recognized for her work related to arsenic, stem cells, and cancer.

The award is for the paper "Arsenic-transformed malignant prostate epithelia can convert noncontiguous normal stem cells into an oncogenic phenotype," which appeared in Environmental Health Perspectives last summer (see story) and was selected as an NTP paper of the year (see summary). Publications competing for this award are judged on the basis of scientific innovation, impact of the research on toxicological sciences, and the scientific impact of the publishing journal, among other factors.

Xu’s paper was considered to contain seminal scientific findings on how arsenic-transformed malignant human prostate epithelial cells impact neighboring human prostate normal stem cells (NSCs), via a transwell co-culture system (see text box).

This transwell system prevented physical contact between the malignant epithelial cells and NSCs, but did allow them to share secreted factors. The results indicate that arsenic-transformed malignant epithelial cells could drive the nearby, but noncontiguous, NSCs into a cancer phenotype, in effect creating cancer stem cells (CSCs) without any actual physical contact.

“This work is a highly significant step forward in our quest for mechanisms in arsenic carcinogenesis,” said Waalkes, who serves as Xu’s mentor. “Throughout the work, Dr. Xu employed clever design, elegant experimentation, and outstanding interpretation of data to produce this article. Her work represents a major advance in defining the role of stem cells during arsenic carcinogenesis.”

Xu won a first place Stem Cells Specialty Section Excellence in Research Award in the postdoctoral category at SOT last year. She also won first place for her research at the North Carolina SOT fall meeting in 2010 (see story) and was just elected the group’s 2013 postdoctoral representative.

(Robin Mackar is the news director in the NIEHS Office of Communications and Public Liaison, and a frequent contributor to the Environmental Factor. SOT Communications/Media Manager Martha Lindauer wrote the SOT press release on Xu’s award.)

Uncovering a mechanism involved in tumor initiation

Xu found that with arsenic-transformed malignant epithelial cells, CSC recruitment appears to occur by malignant cells sending out tumor microenvironmental factors, potentially including interleukin-6, which alone converted NSCs into CSC-like cells and duplicated most responses induced by malignant epithelial cell co-culture.

This recruitment of NSCs into CSCs by arsenic-transformed malignant epithelial cells potentially constitutes a new phenomenon in tumor growth, invasion, dissemination, or field cancerization.

CSCs are thought to be the source of new malignant cells that allow tumors to grow and spread, and they may well be integral to tumor initiation, progression, and metastasis. Inorganic arsenic is a known human carcinogen, but the precise mechanisms are unknown.

The recruitment of NSCs into CSCs by arsenic-transformed malignant epithelial cells may be a key mechanism in arsenic-induced CSC overabundance previously seen in multiple in vivo and in vitro model systems.

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