Researchers from the University of Pennsylvania School of Veterinary Medicine have identified how molecules of microRNA are responsible for the growth of blood vessels in a model for human colon cancer.
The process, called angiogenesis, results in ability of ravenous cancer cells to recruit blood vessels and receive a steady supply of nutrients and oxygen.
The findings, which appear in the online version of Nature Genetics, suggest that these microRNAs might also be a good target for future therapeutics designed to slow the growth of cancer cells.
"These findings also uncover a new role for a well-known cancer-causing gene called MYC," said Andrei Thomas-Tikhonenko, professor in Penn Vet's Department of Pathobiology. "We have discovered that, within a tumor cell, one of the tasks of MYC is to turn loose a particular set of microRNAs, which then becomes responsible for promoting the growth of new blood vessels that nourish the tumor."
MicroRNAs are, as the name implies, short strands of RNA. During the last few years, microRNAs have been found to have a significant role in the process by which genes are translated into proteins. Clusters of microRNA have been "caught" associated with messenger RNA, the intermediary molecule that "instructs" the cell's protein-building machinery. In particular, microRNAs help determine the life-span of messenger RNA and, therefore, how many copies of a protein can be made from a single messenger RNA molecule.
The Penn researchers discovered the role of microRNAs in angiogenesis while studying what makes MYC unique among other cancer-causing genes, or oncogenes. In particular, they were curious why cells with hyperactive MYC don't accumulate particularly fast in Petri dishes yet grow explosively in animal models for the disease
"There are obviously no blood vessels in a Petri dish, so the angiogenic properties of the MYC gene are not advantageous," said Michael Dews, senior researcher in the Thomas-Tikhonenko lab. "In the incubator, the cancer cells grow at normal rates, but in the mouse model you see them recruiting a lot of blood vessels and really taking off. Curiously, this is not the case with some other oncogenes. So, what makes MYC special?"
The MYC protein is known to have a role in determining how certain genes are transcribed into messenger RNAs. To understand the role of MYC in angiogenesis, the Penn researchers used microarray technology to screen MYC-positive and MYC-negative cancerous cells for the presence or absence of 192 known pro- and anti-angiogenesis molecules. They found that, while MYC did not lead to excessive amounts of pro-angiogenesis molecules, it did seem to depopulate an entire family of anti-angiogenesis molecules related to the so-called thrombospondin-1 protein. MYC effectively disabled the brakes that slow angiogenesis.