From OncoLog, October 2013, Vol. 58,
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.
information, talk to your physician, visit www.mdanderson.org, or call askMDAnderson at 877-632-6789.
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