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The tumor cells now gain direct access to the epithelial even clog capillaries due to their big size. Many CTCs
[11]
membrane of the vessels and squeeze into them through can be shed from a given tumor in different locations.
the tight junctions. Once into the bloodstream, they can A given tumor may vary in nature at different locations,
[7]
easily transport to other tissues of the body and invade that is, it may display heterogeneity. CTCs released from
them. An aggressive tumor cell can attach itself to the different locations of a tumor may exhibit discrepancies
endothelial membrane of the vessel and create a “pore” of a given tumor. Thus, CTCs can contribute to a
through which it escapes out and invade the nearby potpourri of heterogeneous cells disgorged from the same
tissue. Other less aggressive tumor cells can use this tumor. [11]
[8]
pore to enter the same tissue and establish a new tumor. Despite consistent efforts, researchers are yet to gather its
Malignant tumors also initiate angiogenesis to enhance caboodle. Of the known properties, one of them is that
blood supply around the tumor and support its growth they undergo epithelial to mesenchymal transition (EMT)
and development. All this time, when several changes as shown in Figure 2. This results in change with respect
[9]
are taking place during the course of tumor growth, an to epithelial markers and other cellular properties. An
[12]
important phenomenon is the shedding of cells from the epithelial cell starts behaving like a mesenchymal cell
primary tumor in the bloodstream as CTCs. These and can detach itself from the parent tissue and become
[10]
cells carry tremendous information about the presence a free fl owing entity. CTCs use this property to invade
of tumor, its growth stage and mutations that it harbors. blood and lymph capillaries and swim freely in them. Not
Due to this vital data, they have enormous applications all CTCs undergo complete EMT; some of them undergo
in the detection, staging and treatment guidance of solid just partial changes or partial EMT. CTCs undergone
tumor malignancies. In this review, we have discussed complete EMT can revert their phenotype by undergoing
about their signifi cance, isolation, enrichment techniques mesenchymal to epithelial transition (MET) out of
and the advancements in the fi eld of molecular biology which some can contribute to micro or macro-metastasis
of CTCs in major types of cancers including breast, leading to cancer progression. When a tumor cell
[13]
prostate, colorectal, and lung cancer.
undergoes reversion by MET, they regain properties
Circulating Tumor Cells of cell adhesion. These cells fi rst adhere to the wall of
capillaries and then evade from them to nearby tissues.
CTCs are described as cells shed by a primary tumor into Since they can now behave as epithelial cells again; they
vasculature and they keep circulating in the blood stream adhere to the target site and start dividing and re-dividing
[10]
of cancer patients. Scientists have tried to decipher giving rise to a new tumor. However, EMT transition
their nature and signifi cance. CTCs are known to be can also lead to a perplexed situation as there is a lot of
circulating in the body fl uids before they metastasize to diversity in the morphological transformations.
various parts of the body even in primary stages of the
[10]
disease. However, they are not easily identifi ed, as Signifi cance of CTCs
they are present in a very small numbers. It is estimated One of the most axiomatic implications of CTCs is that
that a teaspoon of blood might contain just about 5-50 they are minimally invasive indicators. [12,13] Detection
CTCs. CTCs fi rst exuviate from the primary tumor and of CTCs can reveal mint of information rather than just
remain in the blood stream for a while till the time it the presence of a tumor. They can help us to realize
wedges itself in a new tissue as shown in Figure 1. Some the concept of tailor-made medicine. Analysis of CTCs
CTCs can adhere to the wall of capillaries and bunk to
enter a new tissue. While in the blood stream, they might
Figure 1: Cells migrating from primary tumor into blood stream and to a site
of invading another tissue Figure 2: Transition of cells from epithelial to mesenchymal phenotype
Journal of Cancer Metastasis and Treatment ¦ Volume 1 ¦ Issue 2 ¦ July 15, 2015 ¦ 45