Location matters, even for tumors

Written by 
Bill Stallcup, Ph.D.
Close up human Red blood vessel shutterstock_572871130

Location, Location, Location! We often hear this in real estate, but it’s also true in biology. Cells need to be in the right place at the right time to help promote organ development and send the signals that keep our bodies working. But tumors rely on location as well, especially when it comes to angiogenesis—the process they use to recruit new blood vessels to “feed” their growth with oxygen and nutrients.

In the journal Cancers, William Stallcup, Ph.D., a professor in SBP’s NCI-Designated Cancer Center, describes the importance of location for vascular endothelial growth factor (VEGF), a protein that stimulates blood vessel formation.

“VEGF is a major stimulus for the formation of tumor blood vessels,” says Stallcup. “In fact, blocking VEGF has been one idea for slowing tumor growth by cutting off the tumor blood supply. This strategy has not been as successful as researchers had hoped, partly because blood vessel formation and the action of VEGF are both complex processes that we don’t fully understand.”

The vascular cells that form blood vessels are embedded in a fibrous meshwork called the vascular extracellular matrix (ECM). Some forms of VEGF bind tightly to this ECM, while other forms diffuse freely in tissues. The Stallcup lab’s studies reveal that the way VEGF and ECM interact is very important for tumor blood vessel formation.

According to Weon-Kyoo You, Ph.D., a former Stallcup postdoc and first author of the study, “When we looked at brain tumor growth in normal mice, we found that lots of VEGF was bound to the vascular ECM. But when we studied tumor growth in mutant mice that were deficient in ECM assembly, we saw that the VEGF mostly diffused away from tumor blood vessels and was dispersed in the tumor tissue.”

This change in VEGF location had large effects on the structure and function of tumor blood vessels. In normal mice, efficient binding of VEGF to the vascular ECM produced large diameter vessels that were not leaky—and brain tumors grew fast in these mice. In mice with deficient VEGF-ECM interactions, the blood vessels were thin and leaky—and brain tumors grew slowly due to lack of nutrients.

Stallcup concludes that, “We were very surprised at the correlation between healthy ECM, VEGF binding, and tumor growth. Apparently, having the VEGF located right there at the site where it can be readily used by vascular cells is a key factor in producing functional blood vessels.

“These studies add to our understanding of the tactics tumors use to grow, and also give us new clues about how we might be able to thwart cancer progression.”

Read the study here.