Biomedical Engineering Reference
In-Depth Information
function as a tumor suppressor in breast cancer cell lines, where it blocks the
translation of ACTR/AIB1 (co-activator of p160), thus inhibiting ER and E2F1
signaling (Hossain et al., 2006). In most studies, miR-21 has been shown to be
oncogenic; however, in one study in HeLa cervical cancer cells, blocking miR-21
function was shown to significantly increase cancer cell growth, suggesting that in
these cells, miR-21 functions as a tumor suppressor (Cheng et al., 2005a).
6 Cancer Stem Cells and miRNA
Although the identity of cancer stem cells is controversial at this time, there is a
growing consensus that there are sub-populations of cells in solid tumors that have
a higher propensity to give rise to a tumor with features similar to that of the
original tumor. These ''cancer stem cells'' (CSCs) or ''tumor-propagating cells''
(TPCs) are able to initiate orthotopic tumors in xenograft models, even when they
are implanted at very low densities (Reya et al., 2001). These cells have been shown
to be resistant to various cancer therapies (chemotherapeutics and radiation) and
are capable of recreating the tumor microenvironment, including the vasculature
(Bao et al., 2006a,b; Gilbertson and Rich, 2007). Hallmark features of many
tumors with poor prognosis, such as elevated cellular migration and establishing
themselves in a new niche/microenvironment, can be attributed to CSCs or TPCs.
Thus, there is an urgent need to understand the biology of CSCs or TPCs so as to
develop effective cancer therapies where the focus will be on treating the minor
populations of resistant CSCs or TPCs as well as the bulk of the tumor mass. There
are tumors that do not seem to have cancer stem cells, as they are curable through
surgery or other treatments (Polyak and Hahn, 2006) and, perhaps, we can identify
a special niche or microenvironment (paracrine factors, a specific cellular compo-
sition, intrinsic expression profile, or network of factors, including miRNA) in
these tumors that inhibits cancer stem cell proliferation or maintenance.
Most of our current understanding of CSCs is derived from studies done in
areas such as brain tumors and cancers of the hematopoietic system. Cell types
suited for being cancer stem cells include the following: (a) minor self-renewing
multipotent quiescent stem cells that acquire mutations and give rise to tumor;
(b) somewhat restricted progenitor cells targeted by mutations that subse-
quently reacquire features of stem cells and give rise to tumor; and (c) terminally
differentiated cells that dedifferentiate upon gaining mutations and give rise to
tumors (Stiles and Rowitch, 2008). Among all these possibilities, there is
evidence to suggest that, most often, the targets of transforming mutations
are less mature (differentiated) cells. However, cancer stem cells and tumor cell
origin are two independent issues, where CSCs are perhaps the endpoints of the
initial tumorigenic transformation events.
It is well documented that cells in tumors experience a variety of stresses,
including hypoxia, nutrient deprivation, chemicals, and radiation. It is, thus,
very important to look at these factors and their putative role in cancer stem cell
