In a novel study, University of North Carolina and the College of Arts and Sciences scientists have identified a novel mechanism that triggers blood vessel growth.
They have found that vascular networks form and expand by "sprouting" similar to the way trees grow new branches.
The process allows fresh oxygen and nutrients to be delivered to tissues, whether in a developing embryo or a cancerous tumor.
However, the new study has shown that signals can also come from within the blood vessel, pushing new blood vessel sprouts outward.
While analyzing mouse embryonic stem cells and mouse retinas, the researchers found that defects in a protein called Flt-1 lead to abnormal sprouts and poor vessel networks.
Other research recently showed that levels of Flt-1 protein are particularly low in the dilated and leaky blood vessels that supply tumors with oxygen.
"The blood vessels themselves seem to participate in the process guiding the formation of the vascular network," said senior study author Dr Victoria L. Bautch, professor of biology at UNC.
"They do not just passively sit there getting acted upon by signals coming from the outside in. Rather, they produce internal cues that interact with external cues to grow," she added.
The growth of new blood vessels can be stimulated by cascades of events within the cell - known as pathways - the most notable of which centers around the three proteins Flt-1, Flk-1 and VEGF.
During the study, the researchers mixed two different types of mouse embryonic stem cells - one batch with normal Flt-1 protein levels, the other with no Flt-1 protein.
They found that the genetic makeup of the area at the base of the sprout - rather than at the sprout itself - determined whether the sprout behaved normally or abnormally.
"The cells on each side of sprout produce and send out the soluble form of the protein, blocking the sprout from forming anywhere but in one spot and in one direction," says Bautch."
So when the sprout first forms, instead of flopping back onto its parent vessel, it has a corridor to push it forward away from the parent," she added.
The findings have been published in the journal Developmental Cell.