Poster for AACR 2015
Abstract Number: 1608
Session ID: Circulating Tumor
Cells (Poster Section 23)
CTC Categorization:
Subpopulations of CTCs and Their Potential Clinical Significance
Chengsen Xue and Thomas W. Mc Closkey
Research & Development Department, ICON Laboratory Services, Farmingdale, New York
Abstract
miniCTC (CTC-MN)
CTC Cluster (CTC-CL)
A. Regular size CTC
Figure 1. This depiction shows a CTC cluster. Tumor
Circulating tumor cells (CTCs) were previously
considered to be rare events difficult to identify. In
clinical practice, CTC enumeration has now been
recognized for its prognostic value. Furthermore,
as CTC technology has rapidly improved, CTCs
are now readily available for further investigation.
The tumor cells isolated from CTC instruments
may be analyzed for molecular profiles and
mutation screening. Here we propose three new
subsets of CTCs: elongated CTC (EL-CTC),
miniature CTC (Mini-CTC) and cluster CTC (CLCTC). Elongated CTC have an elongated shape
and some of these cells have an enlarged tail
composed of the nucleus. The enlarged tail is
formed during intravasation because of the less
flexible nuclear membrane and these cells
represent highly motile tumor cells. The mini-CTCs
are much smaller than regular tumor cells and may
be dormant and gain the advantage of escaping
immune surveillance. The CTC clusters are formed
by a group of tumor cells and lymphocytes as well
as macrophages. There is strong evidence that
these clusters are highly malignant. These three
subsets are recognized morphologically and their
unique features may directly relate to their
functionality and clinical significance. Additional
investigation in the area of CTC research,
specifically enhanced understanding of CTC
subpopulations, may lead to novel therapeutic
approaches in oncology.
B. MiniCTC
cells are marked in green. The cluster may contain
other cell types, such as lymphocytes (WBC, in blue),
macrophages (in red), and dendritic cells (not shown).
Some reports indicate that certain genes are upregulated in clusters as compared to individual CTCs.
In the CellSearch test every CTC cluster is enumerated
as one CTC. CTC clusters may hold clinical significance
related to augmented metastasis. Studies on the role
of macrophages in metastasis indicate they may exert
paracrine effects as metastasis facilitators . The exact
role of lymphocytes is unclear. It may be interesting to
assess PD1/PDL1 on those cells trapped within cluster.
Figure 3. CTCs present a diverse shape and size. Regular CTCs (left
panel, A) are larger when compared to miniCTCs (right panel, B).
MiniCTC can be up to ten-fold smaller than the size of regular CTCs. The
CellSearch System provides a square box during the process of image
review to define the minimum CTC size requirement (4um). The smallest
CTC shown here (first row of right panel) meets this requirement.
elongated CTC (CTC-EL)
Figure 2. Elongated CTCs have a distinct feature: tails composed by less flexible cellular
nuclei (in purple, the CellSearch System from Janssen Diagnostics assigns this color to DAPI
staining). These CTCs are highly motile, and may also represent a small population of
epithelial-mesenchymal-transition (EMT)-transformed cancer cells .
Table 1. EMT review.
Major progress in the
study of CTCs in the past
several years has focused
on the role of EMT in
tumor metastasis. Here is
a summary of some
features of this transition.
EMT-transformed Cells
Epithelial Cells
Morphology
Elongated, spindle-like
Most are round
shape
Molecular
Profile
VIM, FN1, CDH2, SPARC, CDH1, OCLN, PKP2,
SERPINE1, ACTA2,…...
GJB2, TJP3, KRT18…..
Motility
High
Normal
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Contact: Dr. Chengsen Xue --- chengsen.xue(at)iconplc.com
and
Thomas W. Mc Closkey, PhD --- thomas.mccloskey(at)iconplc.com