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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
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