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| Staging System of Neuroblastoma Based on Tumor Spread |
Undoubtingly, many of us know of the fatal effects of cancer and that
there is currently no cure for it.
Cancer is a group of diseases that are characterized by the
uncontrollable division and growth of abnormal cells. Malignant tumors are formed when cancerous
cells invade other areas of the body using the blood or lymph systems. The spread of cancer throughout the body is
termed metastasis and can eventually cause cancer related deaths. Finding ways to decrease metastasis would yield a decrease in malignancy of tumors.
Although there is not yet a cure for cancer, finding biomarkers can aid
in the early diagnosis and treatment of it, which will hopefully increase the
survival rates of cancer patients.
Dr. Alex Carlisle is neuroscientist at
Inova Fairfax Hospital and manages the Inova-GMU Neuroscience Translational
Research Laboratory partnership. One of
his research focuses is neuroblastoma,
a cancer of the sympathetic nervous system.
Neuroblastoma often occurs in infants and young children and accounts
for about 15% of pediatric cancer deaths.
As with all illnesses, early diagnosis and treatment is critical. Children who have neuroblastoma have
favorable outcomes when diagnosed at age one or younger. Detection of cancer in the earlier stages increases
the likelihood of it being manageable. Cancer
staging consists of assigning numbers from I to IV to a cancer to label its
development. Stage I cancer is an
isolated cancer and increases in severity to stage IV, where the cancer has
spread to other areas of the body. Since
neuroblastoma is spontaneous and the characteristics of neuroblastic tumors
vary from patient to patient, there is a high need for improved prognostic and
therapeutic biomarkers. Dr. Carlisle’s
work has shown that neuroblastoma has a high level of heterogeneity which
influences the expression of CXCR4,
a chemokine receptor. CXCR4 may play a
crucial role in promoting neuroblastoma metastasis.
CXCR4, expressed on the surface of a
variety of cells, is an alpha-chemokine receptor for stromal-derived factor 1
(SDF-1), also called CXCL12. Chemokines
are small glycoprotiens from the cytokine family which direct the movement of
cells to their final destinations.
Chemokines are also conserved and have specific ligand-receptor
interactions. This high fidelity between
the ligand and receptor may have special functions.
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| Ligand-Receptor Relationship Between CXCR4 and SDF-1 |
CXCR4 is known to be a part of HIV
infection and is a co-receptor for binding and entry into CD4+ T cells. However, CXCR4 also plays other biological
roles. It is necessary for normal
neuronal development, particularly neural progenitor cell migration during
embryogenesis. Past research
has shown that the knockout of CXCR4 results in embryos being unable to reach
life and malformation of the dorsal ganglia.
CXCR4 has been clinically associated with the progression of cancer
growth, metastasis, and angiogenesis.
Dr. Carlisle’s lab examined the expression of CXCR4 in neuroblastoma
cells and its relationship with the progression of the disease. Human tissue microscopy and CXCR4 staining
was used to simultaneously observe the expression of CXCR4 in relation to the
progression of neuroblastoma in different patients. It was found that in ganglioneuroma, benign
tumors, CXCR4 expression was low.
Conversely, CXCR4 expression was high in stage IV neuroblastic malignant
tumors. These results suggest that CXCR4
may signal the presence of cancerous cells and their histology. It is somewhat ironic that although CXCR4 is
necessary to the survival of embryos, later on, high expressions of it is
linked to the development of neuroblasoma, which may be fatal.
The aforementioned findings can be
applied clinically to determine the development of neuroblastoma and its tumor growth
progression. Now that a link has been
established between CXCR4 and neuroblastoma, could CXCR4’s expression levels
predict the prognosis of the disease?
More expression of CXCR4 may correlate with higher rates of mortality
while low levels of expression indicate higher rates of survival. This allows the medical field to have more
precise examinations of CXCR4 status and the progression of the disease. Blocking CXCR4 signaling inhibits
neuroblastoma growth and provides therapeutic cures. Plerixafor
(AMD3100) is an FDA approved drug currently being used to counteract the
effects of increasing levels of CXCR4. Increasing
the concentration of Plerixafor results in a reduction in tumor volume and metastasis. Although cancer may not be 100% curable, new
findings, such as those in Dr. Carlisle’s lab, will provide the groundwork for
the development of cures in the future.
How can diagnostic tests be improved to provide closer observations of
biomarkers such as CXCR4? Time is
critical to the development of all diseases.
We cannot afford to waste anymore time.
References:
http://www.ncbi.nlm.nih.gov/pubmed/18847313
https://www.youtube.com/watch?v=lvoCrxLdPno
https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgZCnxOF6fVxUkApyZKyPXhcnZDpxrcD6YIAuODe9jqatmCH6fW8uzkLDgIIVdKoL9ncTTBKsOKFhK4mRZkQe8AdzQhf2JXm19szcRTeP5Wr-J2hpHLuGy-MssZgGCttHLk6SUkKKDyEs0/s1600/Cancer_biomarker_figure.png
https://www.youtube.com/watch?v=lvoCrxLdPno
https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgZCnxOF6fVxUkApyZKyPXhcnZDpxrcD6YIAuODe9jqatmCH6fW8uzkLDgIIVdKoL9ncTTBKsOKFhK4mRZkQe8AdzQhf2JXm19szcRTeP5Wr-J2hpHLuGy-MssZgGCttHLk6SUkKKDyEs0/s1600/Cancer_biomarker_figure.png
