OncoLog

 

From OncoLog, October 2013, Vol. 58, No. 10

In Brief

miR-200 MicroRNAs Slow Tumor Growth

The miR-200 family of microRNAs may hinder angiogenesis and cancer progression in lung, ovarian, kidney, and basal-like breast cancers, according to a recent preclinical study.

MicroRNAs, including the miR-200 family, regulate gene activation and expression. “We initially looked at miR-200 because we have an approach for delivering these molecules with nanoparticles, and miR-200 is known to inhibit the epithelial-mesenchymal transition associated with cancer progression and metastasis,” said Anil Sood, M.D., a professor in the Departments of Gynecologic Oncology and Cancer Biology at The University of Texas MD Anderson Cancer Center and the senior author of the study’s report.

To clarify the mechanisms of miR-200’s regulation of cancer growth and spread, Dr. Sood and his colleagues first analyzed tumor samples from The Cancer Genome Atlas for expression of all five miR-200 family members. Higher expression of miR-200 in lung, ovarian, kidney, or basal-like breast cancers was associated with longer overall survival.

An analysis of miR-200 expression in cancer cell lines revealed an angiogenesis network involving the cytokines interleukin-8 (IL-8) and CXCL1. Further analysis of publicly available microarray databases showed higher IL-8 and CXCL1 levels in lung, ovarian, kidney, and basal-like breast cancers than those in luminal breast cancer subtypes. Also, high IL-8 levels were associated with poor survival rates in patients with lung, ovarian, kidney, and basal-like breast cancers but not those with luminal breast cancer. These findings led to experiments in which miR-200 treatment decreased levels of IL-8 and CXCL1 in lung, ovarian, kidney, and basal-like breast cancer cell lines.

When these cancers were grown in mice, miR-200 delivered in fatty nanoparticles caused steep reductions in tumor size and blood vessel density compared with controls treated with nanoliposomes loaded with nontargeted microRNA. The mice with ovarian cancer also exhibited reductions in circulating IL-8 levels. Two miR-200 members in combination, delivered to the tumor vasculature through chitosan nanoparticles, reduced the size and number of ovarian cancer metastases by 92% compared with controls. In another group of mice with ovarian cancer, the chitosan nanoparticles decreased the primary and metastatic tumor burden and reduced angiogenesis with no apparent toxicity.

The study was reported in the March edition of Nature Communications. The authors wrote that because circulating IL-8 levels strongly correlated with tumor burden, IL-8 may be a biomarker for patients who would benefit from miR-200 therapy.

For more information, talk to your physician, visit www.mdanderson.org, or call askMDAnderson at 877-632-6789.

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