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Molecular
Mechanisms of Glioma Cell Migration and Invasion
Tim
Demuth, Michael E. Berens
TGen,
The Translational Genomics Research Institute, Phoenix, ArizonaUSA
[T.D.]; TGen, The Translational Genomics Research Institute,
Phoenix, ArizonaUSA; Neurogenomics Division, TGen, 400 N. Fifth
Street, Suite 1600, Phoenix, Arizona 85004, USA [T.D., M.E.B.].
Gliomas are the most common
intracranial tumors.
In the US, approximately 15,000 patients die with glioblastoma per
year (CBTRUS 2002).
Despite modern diagnostics and treatments the median survival time
does not exceed 15 months.
However, it has long been observed that after surgical removal, tumors
recur predominantly within 1 cm of the resection cavity.
This is mainly due to the fact that at the time of surgery, cells from
the bulk tumor have already invaded normal brain tissue.
Decades ago Matsukado showed that more than 50% of untreated brain tumors
had already reached the contralateral hemisphere (J Neurosurg 18:
636–644, 1961).
Therefore one of the most important hallmarks of
malignant gliomas is their invasive behavior.
Dandy already recognized the highly invasive
characteristics of this tumor type and performed hemispherectomy
in patients with preoperative hemiplegia (J Am Med Assoc 90: 823–825, 1928).
Despite his and others’ heroic efforts, recurrence
was detected as early as 3 months
after surgery (Bell, LJ: J Neurosurg 6: 285–293, 1949), leading to the discontinuation of this radical
approach.
Diffuse gliomas remain a particularly challenging clinical management
problem.
Over the last 20 years no significant increase
in survival of patients suffering from this disease has been
achieved. –167, 2003).
Furthermore, anti-angiogenic drugs have been shown to increase glioma
invasiveness, finally leading to gliomatosis cerebri. (Lamszus et al.: Acta Neurochir Suppl 88: 169–177, 2003).
In
this review we focus on the main features which may underlie the
invasive phenotype of human gliomas, and offer a biological basis
for optimism towards therapeutic advances to come.
Keywords:
cadherin, DAP3, ECM, FAK,
Fnl4, gap junction, glioma, GTPases, integrin, invasion, invasive
transcriptome, migration, NCAM, P311, PI3-K, SPARC
Copyright
©
2004 Kluwer Academic Publishers.
All
rights reserved
Source: http://ipsapp007.kluweronline.com/IPS/content/ext/x/J/5042/I/125/A/7/abstract.htm
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