In cancer, molecular signals that recruit blood vessels also trigger metastasis
Metastatic cancer cells have the ability to recruit blood vessel cells they send out multiple signals that cause endothelial cells to arrive at the incipient metastatic site, says the studys senior author, Sohail Tavazoie, head of the Elizabeth and Vincent Meyer Laboratory of Systems Cancer Biology. Our new work shows that a microRNA known as miR-126 blocks metastasis by suppressing several genes that promote this process. These genes both increase blood vessels and trigger metastasis.
MiR-126 is one of three microRNAs that Tavazoie and his colleagues had previously identified as being linked to breast cancer metastasis. In work he published in 2008, Tavazoie established that miR-126 acts as a metastasis suppressor in mice, and found that breast cancer patients whose tumors contained very low levels of miR-126 had a much higher likelihood of having their cancer spread than did patients with higher levels of miR-126.
The new work suggests that blood vessel cells are a major reason why. Working with human tumor cells in vitro, as well as with mice, first authors Kim Png, a graduate student, and Nils Halberg, a postdoctoral fellow, found that miR126 blocks three novel cancer genes, known as IGFBP2, MERTK and PITPNC1. Although each of the genes works on distinct pathways discovered by this group, the results are the same: more endothelial cells and increased blood vessel formation in the metastases.
But whats most remarkable about the results, the researchers say, is what happens after the blood vessels form. The teams experiments show that enhanced expression of these genes increases metastasis in mice. And when they went further, testing clinical samples of human tumors for expression of the three genes, they found a clear correlation: patients whose tumors had higher expression of these genes were more prone to relapse.
The endothelial cells arent just providing blood flow to the cancer cells, Tavazoie says, they are somehow triggering the metastatic process, providing a signal back to the cancer cells that allows them to initiate metastatic colonies. Our work reveals a novel and non-canonical role for blood vessel cells in cancer biology, and one that we need to better understand in order to rationally target and prevent metastasis.