Nav: Home

A common nerve protein elevated in aggressive neuroblastomas

October 12, 2016

WASHINGTON - A protein produced by nerve cells appears to be elevated in the blood of those with an aggressive form of neuroblastoma. The finding, published online October 12 in the American Journal of Pathology, could potentially lead to a prognostic test for the disease or be used to monitor its progress.

Neuroblastoma is a pediatric cancer with varying types, ranging from spontaneously regressing to untreatable fatal tumors. Consequently, treatment strategies vary significantly between patients, encompassing different approaches including observation alone or intensive chemo- and radiotherapy.

"Given the severe late effects of anti-cancer treatment administered to infants and children, proper disease stratification is of utmost importance for neuroblastoma patients," explains Joanna Kitlinska, PhD, associate professor in the department of biochemistry and molecular & cellular biology at Georgetown University Medical Center.

Because of their neuronal origin, neuroblastomas synthesize and release neuropeptide Y (NPY), a small protein normally secreted from mature nerves. In previous research, Kitlinska and her colleagues have shown that NPY, acting via its Y2 and Y5 receptors (Y2R and Y5R), is crucial for maintaining neuroblastoma growth and protecting the tumors from chemotherapy.

"To confirm the clinical relevance of our earlier work and assess NPY and its receptors as potential prognostic factors, we performed clinical study on tissue samples and serum from 87 neuroblastoma patients," Kitlinska explains.

"We have found that NPY is released from aggressive neuroblastoma tumors into the blood, which results in its elevated serum concentrations. These high systemic levels of NPY are associated with several adverse prognostic factors for neuroblastoma and worse survival of neuroblastoma patients. "

She adds that high NPY release is a strong marker of metastatic disease, while the Y5R is present preferentially in invasive neuroblastoma cells. Also, patients with elevated NPY at diagnosis were more likely to have a disease relapse in the future.

"These results support the previously described crucial role for NPY in neuroblastoma biology, and suggest its contribution to the disease dissemination and resistance to therapy. Thus, our study validates the NPY system as a potential therapeutic target and potential prognostic marker for neuroblastoma," she says.

"In contrast to complex genetic analyses currently utilized to assess risk of the disease, the measurement of NPY levels in blood can be converted to a readily available analytical test. Using such easily accessible clinical material may also allow for minimally invasive longitudinal monitoring of the disease progression," Kitlinska explains.

"If confirmed by further prospective studies, this finding may have a significant impact on the clinical management of patients with neuroblastoma," she concludes.
-end-
In addition to Kitlinska, authors include Chris Albanese, Susana Galli, Chao Yang, Jessica Tsuei, Jason Tilan, Emily Trinh, Sung-Hyeok Hong, Olga C. Rodriguez, Hongkun Wang and Yi-Chien Lee of Georgetown; Arlene Naranjo and Collin Van Ryn from the University of Florida Children's Oncology Group; and Ewa Izycka-Swieszewska of Medical University of Gda?sk, Poland.

Kitlinska and her co-authors report having no personal financial interests related to the study.

Samples of neuroblastic tumors were obtained from Children's Oncology Group, which also provided statistical support for the study (Naranjo and Van Ryn). The association of high NPY and Y5R expression with metastatic phenotype of the tumor cells was confirmed in an animal model of neuroblastoma, in collaboration with the Georgetown Lombardi Comprehensive Cancer Center Preclinical Imaging Research Laboratory (Albanese and Rodriguez).

The study was supported by grants from the National Institutes of Health (UL1TR000101 1RO1CA123211, 1R03CA178809, 1R01CA197964, 1R21CA198698, U10CA180899 and P30-CA051008.)

About Georgetown University Medical CenterGeorgetown University Medical Center (GUMC) is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC's mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization, which accounts for the majority of externally funded research at GUMC including a Clinical and Translational Science Award from the National Institutes of Health. Connect with GUMC on Facebook (Facebook.com/GUMCUpdate), Twitter (@gumedcenter) and Instagram (@gumedcenter).

Georgetown University Medical Center

Related Neuroblastoma Articles:

New biomarker assay detects neuroblastoma with greater sensitivity
Investigators at The Saban Research Institute of Children's Hospital Los Angeles have developed and tested a new biomarker assay for quantifying disease and detecting the presence of neuroblastoma even when standard evaluations yield negative results for the disease.
New research points to potential for more targeted treatments of neuroblastoma tumors
Genetic variations appear to pre-dispose children to developing certain severe forms of neuroblastoma, according to new research by the University of Chicago Medicine.
Two investigational antitumor agents work better together against MPNST and neuroblastoma
A new study published last week in Oncotarget demonstrates that the combined usage of Aurora A kinase inhibitor (alisertib) and HSV1716 results in significantly increased antitumor efficacy in models of malignant peripheral nerve sheath tumor (MPNST) and neuroblastoma.
CHLA awarded grant to study immunotherapy resistance in neuroblastoma
A team of investigators at Children's Hospital Los Angeles has received a major, three-year grant from the V Foundation for Cancer Research to study the effects of chemoimmunotherapy in children with neuroblastoma.
Combination therapy shows promise in fighting neuroblastoma
A study by a multidisciplinary team of researchers from The Saban Research Institute of Children's Hospital Los Angeles sheds further light on the role of the cytokine TGFβ1 in the growth of neuroblastoma, and suggests the possibility for a small molecule drug/antibody combinatorial therapy to treat this cancer.
Nuclear protein causes neuroblastoma to become more aggressive
Aggressive forms of neuroblastoma contain a specific protein in their cells' nuclei that is not found in the nuclei of more benign forms of the cancer, and the discovery, made through research from the University of Rochester Medical Center, could lead to new forms of targeted therapy.
Loss of a microRNA family, let-7, found key in neuroblastoma
A study led by researchers at Dana-Farber/Boston Children's Cancer and Blood Disorders Center, finds that a microRNA called let-7 plays a central role in curbing neuroblastoma and could focus efforts to find a targeted, nontoxic alternative to chemotherapy.
Doctors unleash new weapon to fight pediatric neuroblastoma
After the first year of receiving the novel treatment combination, more than half of children with relapsed neuroblastoma saw either a complete or partial remission -- a 53 percent response rate compared to the typical 10 to 12 percent response rate.
Dual stem-cell transplant improves outlook for children with high-risk neuroblastoma
Children with high-risk neuroblastoma whose treatment included two autologous stem-cell transplants were more likely to be free of cancer three years later than patients who underwent a single transplant, a Phase 3 clinical trial has found, according to research presented at the annual meeting of the American Society of Clinical Oncology.
Investigational immunotherapy drug shrinks tumors in high-risk neuroblastoma patients
St. Jude Children's Research Hospital investigators report promising preliminary results at the annual meeting of ASCO for an experimental monoclonal antibody when combined with chemotherapy for newly diagnosed patients.

Related Neuroblastoma Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...