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Image by Louis Heiser
and Robert Ackland
Scientists say they have developed a model that provides new insight into chaotic angiogenesis, a hallmark of cancer.
The model shows how proteins involved in angiogenesis communicate with each other and how tumors take charge of the protein signaling chain that controls blood vessel growth.
The work, published in PNAS, suggests that Jagged ligands play a major role in the chaotic vessel growth observed around tumors.
In normal growth, an endothelial cell sprouts from an existing blood vessel as a tip. Others that follow the tip cell become the stalk cells that ultimately form vessel walls. The Notch signaling pathway directs the endothelial cell’s decision to become a tip or stalk.
Notch receptors bind with Delta ligand or Jagged ligand molecules produced by cells. How they interact determines the cell’s fate.
When Notch and Delta bind, they prompt a few cells to be tips and adjacent ones to be stalks. The Notch-Delta pathway has been studied extensively and is the target of many angiogenesis inhibitors now in use, according to the scientists.
“We wondered exactly what Notch-Jagged signaling does that is not done in Notch-Delta signaling,” said study author Marcelo Boareto, PhD, of the Swiss Federal Institute of Technology in Zurich.
“We find that when the cells communicate mostly via Jagged, we see a new kind of cell that is not exactly tip and not exactly stalk, but somewhere in between. This compromised cell is the major difference between normal and tumor angiogenesis and suggests that if Notch-Jagged signaling can be somehow suppressed without affecting Notch-Delta, we can probably disrupt tumor angiogenesis.”
The scientists found the tip/stalk hybrid cells do form new blood vessels, but these vessels rarely mature.
“High levels of Jagged in the environment can trigger the formation of blood vessels that are useful to the tumor: fast-developing, leaky, and spread chaotically all over the tumor mass,” Dr Boareto said.
“Tumors don’t have to wait for the vessels to develop,” added study author José Onuchic, PhD, of Rice University in Houston, Texas. “They take advantage of the leakiness of the structure.”
The scientists’ model also takes into account the effect of vascular endothelial growth factor, which triggers angiogenesis and is overexpressed by tumor cells.
“It is very interesting how the tumor hijacks this important mechanism, which is needed for the development of a functional vessel, and amplifies it to generate pathological angiogenesis that leads to uncontrolled growth,” Dr Onuchic said. 
Image by Louis Heiser
and Robert Ackland
Scientists say they have developed a model that provides new insight into chaotic angiogenesis, a hallmark of cancer.
The model shows how proteins involved in angiogenesis communicate with each other and how tumors take charge of the protein signaling chain that controls blood vessel growth.
The work, published in PNAS, suggests that Jagged ligands play a major role in the chaotic vessel growth observed around tumors.
In normal growth, an endothelial cell sprouts from an existing blood vessel as a tip. Others that follow the tip cell become the stalk cells that ultimately form vessel walls. The Notch signaling pathway directs the endothelial cell’s decision to become a tip or stalk.
Notch receptors bind with Delta ligand or Jagged ligand molecules produced by cells. How they interact determines the cell’s fate.
When Notch and Delta bind, they prompt a few cells to be tips and adjacent ones to be stalks. The Notch-Delta pathway has been studied extensively and is the target of many angiogenesis inhibitors now in use, according to the scientists.
“We wondered exactly what Notch-Jagged signaling does that is not done in Notch-Delta signaling,” said study author Marcelo Boareto, PhD, of the Swiss Federal Institute of Technology in Zurich.
“We find that when the cells communicate mostly via Jagged, we see a new kind of cell that is not exactly tip and not exactly stalk, but somewhere in between. This compromised cell is the major difference between normal and tumor angiogenesis and suggests that if Notch-Jagged signaling can be somehow suppressed without affecting Notch-Delta, we can probably disrupt tumor angiogenesis.”
The scientists found the tip/stalk hybrid cells do form new blood vessels, but these vessels rarely mature.
“High levels of Jagged in the environment can trigger the formation of blood vessels that are useful to the tumor: fast-developing, leaky, and spread chaotically all over the tumor mass,” Dr Boareto said.
“Tumors don’t have to wait for the vessels to develop,” added study author José Onuchic, PhD, of Rice University in Houston, Texas. “They take advantage of the leakiness of the structure.”
The scientists’ model also takes into account the effect of vascular endothelial growth factor, which triggers angiogenesis and is overexpressed by tumor cells.
“It is very interesting how the tumor hijacks this important mechanism, which is needed for the development of a functional vessel, and amplifies it to generate pathological angiogenesis that leads to uncontrolled growth,” Dr Onuchic said.
Image by Louis Heiser
and Robert Ackland
Scientists say they have developed a model that provides new insight into chaotic angiogenesis, a hallmark of cancer.
The model shows how proteins involved in angiogenesis communicate with each other and how tumors take charge of the protein signaling chain that controls blood vessel growth.
The work, published in PNAS, suggests that Jagged ligands play a major role in the chaotic vessel growth observed around tumors.
In normal growth, an endothelial cell sprouts from an existing blood vessel as a tip. Others that follow the tip cell become the stalk cells that ultimately form vessel walls. The Notch signaling pathway directs the endothelial cell’s decision to become a tip or stalk.
Notch receptors bind with Delta ligand or Jagged ligand molecules produced by cells. How they interact determines the cell’s fate.
When Notch and Delta bind, they prompt a few cells to be tips and adjacent ones to be stalks. The Notch-Delta pathway has been studied extensively and is the target of many angiogenesis inhibitors now in use, according to the scientists.
“We wondered exactly what Notch-Jagged signaling does that is not done in Notch-Delta signaling,” said study author Marcelo Boareto, PhD, of the Swiss Federal Institute of Technology in Zurich.
“We find that when the cells communicate mostly via Jagged, we see a new kind of cell that is not exactly tip and not exactly stalk, but somewhere in between. This compromised cell is the major difference between normal and tumor angiogenesis and suggests that if Notch-Jagged signaling can be somehow suppressed without affecting Notch-Delta, we can probably disrupt tumor angiogenesis.”
The scientists found the tip/stalk hybrid cells do form new blood vessels, but these vessels rarely mature.
“High levels of Jagged in the environment can trigger the formation of blood vessels that are useful to the tumor: fast-developing, leaky, and spread chaotically all over the tumor mass,” Dr Boareto said.
“Tumors don’t have to wait for the vessels to develop,” added study author José Onuchic, PhD, of Rice University in Houston, Texas. “They take advantage of the leakiness of the structure.”
The scientists’ model also takes into account the effect of vascular endothelial growth factor, which triggers angiogenesis and is overexpressed by tumor cells.
“It is very interesting how the tumor hijacks this important mechanism, which is needed for the development of a functional vessel, and amplifies it to generate pathological angiogenesis that leads to uncontrolled growth,” Dr Onuchic said.