The findings partly explain why drugs designed to treat cancer by strangling its blood supply have been disappointing when used alone and why those treatments are more effective when combined with traditional chemotherapy.
Despite their rapid progression, tumors fed by more normal vascular were also more vulnerable to the effects of standard chemotherapy drugs, the team reports in this week’s early online edition of the journal Nature.
Nascent tumors take off as new blood vessels invade, an event called angiogenesis that many see as key to the development of malignancy. But those pathological vessels form tangled structures that are far from normal.
“Tumor blood vessels become more chaotic, disorganized and leaky,” said Randall S. Johnson, professor of molecular biology at UC San Diego who led the study. “They become dysfunctional in many ways as a blood vessel network.”
Cellular secretions within tumors promote the invasion. The first drugs designed to curtail cancer’s blood supply targeted one of these, called VEGF for vascular endothelial growth factor. Inflammatory cells, which infiltrate many types of tumors, provide one source of VEGF.
Johnson’s team created a strain of mice in which most inflammatory cells were missing the gene for VEGF, then cross-bred them with a strain that reliably develops mammary tumors and is commonly used to study breast cancer.
“The blood vessels look more organized and less leaky in the engineered mice,” said Christian Stockmann, a molecular biology postdoctoral fellow and the first author of the paper.
The blood supply to tumors in these mice was also sparse compared to mice with intact VEGF genes.
“A lot of these classic hallmarks of tumor blood vessels disappeared when the inflammatory cells couldn’t make VEGF,” Johnson said.
But the cancer grew faster.
All of the mice developed tumors, but at 20 weeks of age, those with low levels of VEGF from inflammatory cells had larger growths that were more likely to have progressed to a later stage of cancer.
“The tumors seemed much happier when they didn’t have this chaotic vasculature,” Johnson said.
The scientists also injected a cancerous cell line into normal and engineered mice and found that the introduced cells invaded normal tissues more readily without VEGF from inflammatory cells and developed more normal blood supplies.
The tumors that formed were also more susceptible to two different chemotherapy drugs in the mice lacking VEGF from inflammatory cells.
By identifying the cellular source of the critical factor for one pathology associated with cancer, the researchers say their findings may open new avenues for treatment.
The National Institutes of Health funded the research.
Randall Johnson | EurekAlert!
Biofilm discovery suggests new way to prevent dangerous infections
23.05.2017 | University of Texas at Austin
Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...
23.05.2017 | Event News
22.05.2017 | Event News
17.05.2017 | Event News
23.05.2017 | Physics and Astronomy
23.05.2017 | Life Sciences
23.05.2017 | Medical Engineering