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Retinoic Acid May Spur Tumor Vessel Growth

Treating breast cancer cells induces endothelial-specific genes, may lead to vasculogenic properties

MONDAY, July 21 (HealthDay News) -- Treating SKBR-3 breast cancer cells with retinoic acid can encourage the growth of extensive network structures and induces endothelial genes, suggesting a method of creating blood supply to tumors, according to research published online July 16 in PLoS ONE.

Yoshimi Endo, M.D., Ph.D., of Georgetown University in Washington, D.C., and colleagues treated SKBR-3 cells in Matrigel with 9-cis-retinoic acid (9-cis-RA), and colonies of fused cells with sinus-like structures developed. In addition, the 9-cis-RA upregulated a number of endothelial-specific genes, including Cox-1, ER81, and VE-cadherin, the latter of which is known to play an important role in angiogenesis.

When cultured with human umbilical vein endothelial cells, the retinoic acid-treated SKBR-3 cells could develop mixed vessel-like structures, the researchers report. This implies that retinoic acid may trigger endothelial-like transdifferentiation in some breast cancer cells that may permit the creation of mixed vessels with the host vasculature, the authors write.

"In summary, we demonstrated that 9-cis-RA induces endothelial-like transdifferentiation in SKBR-3 cells. These phenotypic changes are accompanied by significant induction of the endothelial genetic program. VE-cadherin plays a central role in these morphological alterations, and we found that both Sox-9 and ER81 bind to VE-cadherin promoter and participate in its transcriptional induction by retinoic acid. These data may explain the mixed results of clinical trials using various vitamin A analogues, and bring up the rather disturbing notion that treatments with retinoids might stimulate certain tumor cells to acquire vasculogenic properties," the authors conclude.

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