Navigation Links
Scripps Research scientists reveal how white blood cell promotes growth and spread of cancer

LA JOLLA, CA August 31, 2011 - Scientists at The Scripps Research Institute have shown that a particular white blood cell plays a direct role in the development and spread of cancerous tumors. Their work sheds new light on the development of the disease and points toward novel strategies for treating early-stage cancers.

The study was published in September 2011 print issue of the American Journal of Pathology.

Scripps Research Professor James Quigley, Staff Scientist Elena Deryugina, and colleagues had previously demonstrated that white blood cells known as neutrophilsbone marrow-derived cells that function as "first responders" at sites of acute inflammationpromote the growth of new blood vessels in normal, healthy tissue.

The team has now tied these cells to the induction and growth of new blood vessels in malignant tumors and to the spread of tumor cells through those newly formed vessels. The scientists have also uncovered some of the mechanisms underpinning this processwhich could be interrupted by properly targeted drugs.

Potent and Uninhibited

The Scripps Research team has been particularly interested in neutrophils, in part because several studies have demonstrated a link between elevated neutrophil levels and high rates of tumor invasion among cancer patients. Mounting evidence has also indicated that neutrophils play a particularly important role during the early stages of tumor development.

"During tumor development, neutrophils appear to be one of the first inflammatory cell types on the scene," said Deryugina, who spearheaded the new study.

The researchers have been especially interested in the blood vessel-forming or "angiogenic," powers of neutrophils, which stem from a special enzyme they produce known as MMP-9 (matrix metalloproteinase type 9). The enzyme is, in fact, synthesized by a number of different types of white blood cells and has long been linked to tumor development. But the particular form synthesized by neutrophils is especially potent, in part because it does not come bound up with the natural inhibitory regulating agents that other cells supply.

Whereas other types of white blood cells only manufacture the enzyme later and invariably deliver it in combination with one of its natural inhibitors, neutrophils come loaded with pre-synthesized MMP-9 in a form that is unencumbered.

Making the Case

In a series of cleverly designed experiments, Quigley, Deryugina, and colleagues established a link between neutrophils, their MMP-9, and the growth and spread of tumors.

The scientists alternately raised and lowered the quantity of neutrophils allowed to flow into two different kinds of early-stage tumors, which had been transplanted into chicken embryos and mice. They also introduced several different versions of the enzyme, sometimes combining it with dampening agents, sometimes not.

By observing the subsequent decrease and increase in the formation of new blood vessels, the Scripps Research team was able to establish that the unique form of the enzyme delivered by neutrophils was directly responsible for heightening the growth of new blood vessels in the tumors. Just as importantly, they were able to determine that the newly formed blood vessels served as "escape routes" or conduits for the spread of tumor cells beyond their initial location.

First, the scientists established that the most aggressive tumorsthat is, the ones that were able to most quickly penetrate the surrounding blood vessels and spread to different areasdepended on their ability to attract large numbers of neutrophils.

The researchers then proceeded to spur the growth of new blood vessels in even relatively nonaggressive tumors by supplying additional quantities of neutrophil-derived enzyme. They also blocked the formation of new vessels with the anti-inflammatory drug ibuprofen and then restored, or "rescued," angiogenesis by pumping in additional enzyme.

Quigley and Deryugina also drastically reduced the influx of neutrophils by neutralizing IL-8 (interleukin 8), the chemical attractant that draws neutrophils to sites of inflammation. Blood vessel formation declined correspondingly, as did the penetration of vessels by tumor cells, clearly linking neutrophils to the development and spread of two different, but highly aggressive, forms of cancer. To further strengthen that link, the researchers again reversed the decline with an infusion of neutrophil-derived enzyme.

"By dampening neutrophil influx into tumors, we dampen angiogenesis, but we also dampen metastasis," Quigley said. "And when we rescue angiogenesis, we also rescue the high metastatic rate of the tumors."

Significantly, only the unregulated, uninhibited version of the enzyme provided by neutrophils reversed the dampening effect caused by reducing inflammation or cutting off the flow of neutrophils. No such rescue occurred when the enzyme was combined with its natural inhibiting agentsthe same molecules that accompany the enzyme when it is delivered by other kinds of white blood cells.

Intriguing Possibilities

The scientists note that the study suggests tumors that engender a strong inflammatory response may be particularly amenable to early-stage treatment by drugs that specifically target neutrophils, whether that means inhibiting the enzyme they deliver or simply preventing them from showing up in the first place.

"It might be best to combat tumor angiogenesis earlier rather than later," Quigley said, adding that "more specifically directed anti-neutrophil agents might be better suited than a general anti-inflammatory."

The Quigley lab continues to investigate.

Contact: Mika Ono
Scripps Research Institute

Related medicine news :

1. Scripps Research scientists define cellular pathway essential to removing damaged mitochondria
2. Scripps Translational Science Institute joins Jackson Laboratory tumor consortium
3. Scripps Research scientists show how shifts in temperature prime immune response
4. CIRM awards Scripps Research Institute scientists $3.5 million
5. Scripps Research wins more than $2 million to study prostate cancer
6. New lupus drug results from Scripps Research technology
7. Scripps Research and MIT scientists discover class of potent anti-cancer compounds
8. Scripps Research study points to liver, not brain, as origin of Alzheimers plaques
9. Scripps Research compound blocks brain cell destruction in Parkinsons disease
10. Scripps Research scientists develop powerful new methodology for stabilizing proteins
11. Scripps Research scientists find measles natural nemesis
Post Your Comments:
(Date:11/28/2015)... ... ... Safe storage for contraceptive devices may not always be easy to find. ... the other from Bradley Beach, New Jersey, there is an easy solution to the ... replace NuvaRings more often than necessary. As such, it affords peace of mind and ...
(Date:11/27/2015)... ... ... There is only one major question facing all law firms in the ... has not been an easy question to answer. Especially when the senior partners and ... don’t share the same discipline around working long hours. , In addition to ...
(Date:11/27/2015)... (PRWEB) , ... November 27, 2015 , ... ... affecting the health care in America. As people age, more care is needed, ... costs are rising, and medical professionals are being overworked. The forgotten part of ...
(Date:11/27/2015)... ... November 27, 2015 , ... Lizzie’s Lice Pickers just announced a special promotion ... off of their purchase of lice treatment product. In addition, customers will receive a ... company spokesperson. “Finding lice is a sure way to ruin the holidays, so we ...
(Date:11/27/2015)... ... November 27, 2015 , ... Consistent with the Radiology ... Building Better Radiology Marketing Programs meeting will showcase some of the best ... at Caesars Palace in Las Vegas with a pre-conference session on a collaborative ...
Breaking Medicine News(10 mins):
(Date:11/26/2015)... Países Bajos, November 26, 2015 ... fotodinámica de Bremachlorin para el cáncer avanzado.   ... con la terapia fotodinámica de Bremachlorin para el cáncer ... enfoque combina la inmunoterapia con la terapia fotodinámica de ... Clinical Cancer Research . --> Clinical Cancer ...
(Date:11/26/2015)... UTRECHT , Nederland, November 26, 2015 ... --> Een nieuwe aanpak combineert ... van gevorderde kanker. ... -->      (Photo: ... van het Leids Universitair Medisch Centrum (LUMC) ...
(Date:11/26/2015)... 3D bioprinting market is expected ... new report by Grand View Research Inc. Rising prevalence of ... kidney transplantation is expected to boost the market growth, as ... transplantation. --> 3D bioprinting market is expected ... new report by Grand View Research Inc. Rising prevalence of ...
Breaking Medicine Technology: