Tumorigenic role of podoplanin in esophageal squamous-cell carcinoma
Background. Podoplanin, a mucin-type transmembrane glycoprotein, is thought to be one of the cancer stem cell markers for squamous-cell carcinoma of the vulva. The objectives of the present study were to examine the role of podoplanin in esophageal squamous-cell carcinoma (ESCC). Methods. Expr...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Society of Surgical Oncology
2010
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| Subjects: | |
| Online Access: | http://irep.iium.edu.my/12086/ http://irep.iium.edu.my/12086/ http://irep.iium.edu.my/12086/ http://irep.iium.edu.my/12086/1/Tumorigenic_Role_of_Podoplanin_in_Esophageal_Squamous-Cell_Carcinoma.pdf |
| Summary: | Background. Podoplanin, a mucin-type transmembrane
glycoprotein, is thought to be one of the cancer stem cell
markers for squamous-cell carcinoma of the vulva. The
objectives of the present study were to examine the role of
podoplanin in esophageal squamous-cell carcinoma
(ESCC).
Methods. Expression of podoplanin was examined immunohistochemically
in 61 cases of ESCC that had not been
treated with chemotherapy or radiotherapy before surgery.
Because cancer stem-cell quantities have been reported to
increase with chemotherapy and radiotherapy, cases in
patients who did not receive such prior therapies were
included in this study. Cases with[10% tumor cells showing
signals for podoplanin were categorized as podoplanin high,
and the others were classified as podoplanin low. The effects
of podoplanin on the behavior of cancer cells were evaluated
in ESCC cell lines in which podoplanin expression was
knocked down.
Results. To examine whether podoplanin could be used as
a cancer stem cell marker for ESCC, podoplanin-positive
and podoplanin-negative fractions were sorted separately
from the ESCC cell line and cultured. Podoplanin-positive
ESCC cells yielded both podoplanin-positive and podoplanin-
negative cells, whereas few cells were obtained from
podoplanin-negative ESCC cells. When podoplanin
expression was knocked down, ESCC cell lines became
vulnerable to anticancer drugs and showed defective
invasion and tumorigenic activities. Nineteen (31.1%) of
61 cases were categorized as podoplanin high. Podoplaninhigh
cases were correlated with T category, stage of disease,
lymphatic and vascular invasion, recurrence, and
prognosis of patients. Podoplanin-low cases showed better
overall and disease-free survival.
Conclusions. There is a role for podoplanin in tumorigenesis
and malignant progression in ESCC.
Cancer cells comprise a heterogeneous group of cells,
among which only a small population of cells possesses the
ability to reconstitute a whole tumor.1–3 This population,
called cancer stem cells (CSCs), efficiently forms colonies
in semisolid culture and is xenotransplantable in nonobese
diabetic/severe combined immunodeficiency (NOD/SCID)
mice.4 CSCs were first identified in leukemia and subsequently
isolated from solid tumors, such as those of breast,
brain, prostate, melanoma, colon, pancreas, head/neck,
liver, and gastric cancers.5–15 CSCs are known to be
resistant to chemotherapy and radiotherapy and are more
invasive than non-CSCs.
Recognition of CSCs and their efficient elimination may
be a valuable strategy for treatment of cancers. Therefore,
studies to search for markers of CSCs have been performed.
First, successful isolation of CD34? CD38-
leukemic stem cells was reported.5 However, subsequent
studies showed that markers for CSCs differ among cancers
originating from different organs. Atsumi et al. reported
that podoplanin, a mucin-type transmembrane glycoprotein,
is a possible candidate CSC marker for squamous-cell
carcinoma (SCC).16 Cultured cells from the SCC cell line
A431, which is derived from the vulva, consist of two
populations: podoplanin-positive and podoplanin-negative
cells. CSCs are known to produce both CSC and non-CSC,
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