Biomedical Engineering Reference
In-Depth Information
Scientists are currently dissecting the various cellular and protein components of the
niche to identify the critical parts that maintain cancer stem cells [
27
] . This may
help identify new therapeutic targets. Yang and Wechsler-Reya announced that this
work “highlights the importance of the vascular microenvironment in brain tumor
growth” [
33
]. Brain cancer stem cells are maintained within vascular niches.
Although these cells may be resistant to conventional treatment, preliminary studies
suggest that antiangiogenic drugs can block tumor growth. Cancers share more
properties of normal developing tissues than we may have appreciated. This work
opens up new avenues for treatments, but suggests also that we need to work hard
to define truly how cancers and normal tissues differ [
27
] .
Gilbertson and associates investigated whether brain tumor stem cells develop
within niche microenvironments in the brain vasculature. The majority of cancer
stem cells in brain tumors were closely associated with tumor capillaries [
27
] . In
vitro, brain tumor stem cells associated rapidly with endothelial vascular tubes,
forming close contacts along their lengths, the results indicate [
32
] . Further
experiments showed that endothelial cells maintained self-renewing and undif-
ferentiated brain tumor cells and promoted the propagation of brain tumors
in vivo. Depletion of brain tumor blood vessels effectively eradicated the popula-
tion of self-renewing tumor cells, the report indicates. This led investigators to
propose “that antiangiogenic drugs arrest brain tumor growth, at least in part, by
disrupting a vascular niche microenvironment that is critical for the maintenance
of cancer stem cells” [
33
] .
By recent advance in fundamental knowledge about NSCs and brain tumors
(BT), a small fraction of tumor cells within malignant BT has been found to show
strikingly similar characteristics with normal NSC. Interestingly, only this subset of
tumor cells, called “cancer stem cells,” can initiate the entire malignant tumor and
further cause metastasis to other organs, while the rest of a large heterogeneous
population in BT does not. This “stem cell” in tumor was first identified in acute
myeloblastic leukemia with significant similarity to normal HSC, and the breast
cancer was the first solid cancer, which was found to contain stem cell fraction.
With regard to BT, two independent studies including group led by Prof. Harley I.
Kornblum, Pharmacology, UCLA have shed light on the stem cell population in
some of pediatric malignant tumors in 2003 [
34
]. Several studies from other groups
have succeeded in reproduction of the existence of the “brain tumor stem cells”
since then [
35
] .
Clinical Signi fi cance of Identi fi cation of Cancer Stem Cells
After the isolation of stem cells in BT, scientists have started to identify the critical
regulator genes of the stem cells in BT (
http://www.who.int/cardiovascular_
diseases/resources/atlas/en/
) [
36-
42
]. This project was based on one hypothesis; by
blocking the critical regulator of brain tumor stem cells, they should be able to stop
the malignant tumors to proliferate, keep growing, and invading into the adjacent
normal brain structures, and eventually, kill the patients with malignant tumors.
