24 research outputs found
The PTEN Phosphatase Controls Intestinal Epithelial Cell Polarity and Barrier Function: Role in Colorectal Cancer Progression
The PTEN phosphatase acts on phosphatidylinositol 3,4,5-triphosphates resulting from phosphatidylinositol 3-kinase (PI3K) activation. PTEN expression has been shown to be decreased in colorectal cancer. Little is known however as to the specific cellular role of PTEN in human intestinal epithelial cells. The aim of this study was to investigate the role of PTEN in human colorectal cancer cells.Caco-2/15, HCT116 and CT26 cells were infected with recombinant lentiviruses expressing a shRNA specifically designed to knock-down PTEN. The impact of PTEN downregulation was analyzed on cell polarization and differentiation, intercellular junction integrity (expression of cell-cell adhesion proteins, barrier function), migration (wound assay), invasion (matrigel-coated transwells) and on tumor and metastasis formation in mice. Electron microscopy analysis showed that lentiviral infection of PTEN shRNA significantly inhibited Caco-2/15 cell polarization, functional differentiation and brush border development. A strong reduction in claudin 1, 3, 4 and 8 was also observed as well as a decrease in transepithelial resistance. Loss of PTEN expression increased the spreading, migration and invasion capacities of colorectal cancer cells in vitro. PTEN downregulation also increased tumor size following subcutaneous injection of colorectal cancer cells in nude mice. Finally, loss of PTEN expression in HCT116 and CT26, but not in Caco-2/15, led to an increase in their metastatic potential following tail-vein injections in mice.Altogether, these results indicate that PTEN controls cellular polarity, establishment of cell-cell junctions, paracellular permeability, migration and tumorigenic/metastatic potential of human colorectal cancer cells
Thrombospondin-1 expression in urothelial carcinoma: prognostic significance and association with p53 alterations, tumour angiogenesis and extracellular matrix components
Protocadherin 7 is overexpressed in castration resistant prostate cancer and promotes aberrant MEK and AKT signaling
Immunohistochemical expression of superoxide dismutase (MnSOD) anti-oxidant enzyme in invasive breast carcinoma
The most important cellular protective
mechanisms against oxidative stress are antioxidant
enzymes. Their action is based on decomposal of
reactive oxygen species (ROS) and their transformation
to H2O2. Within the mitochondria manganese superoxide
dismutase (MnSOD) affords the major defense against
ROS.
In this study we investigated tissue sections from
101 breast carcinomas for the immunohistochemical
expression of MnSOD protein and these results were
assessed in relation to various clinicopathological
parameters, in order to clarify the prognostic value of
this enzyme. The possible relationship to hormone
receptor content, anti-apoptotic protein bcl-2, p53 and
cell proliferation was also estimated.
High expression levels were observed, as 79/101
(78,2%) cases expressed strong immunoreactivity. In this
study MnSOD increased in a direct relationship with
tumor grade and is therefore inversely correlated with
differentiation (p=0.0004). Furthermore, there was a
strong positive correlation between MnSOD expression
and p53 protein immunoreactivity (p=0.0029). The
prognostic impact of MnSOD expression in determining
the risk of recurrence and overall survival with both
univariate (long-rang test) and multivariate (Cox
regression) methods of analysis was statistically not
significant.
These results indicate that neoplastic cells in breast carcinomas retain their capability to produce MnSOD
and thus protected from the possible cellular damage
provoked by reactive oxygen species. In addition,
MnSOD content varies according to the degree of
differentiation of breast carcinoma
Thrombospondin-1 expression in urothelial carcinoma: Prognostic significance and association with p53 alterations, tumour angiogenesis and extracellular matrix components
Background: Thrombospondin-1 (TSP-1) is an extracellular matrix component glycoprotein, which is known to be a potent inhibitor of angiogenesis and may be important in cancer invasiveness. We examined the TSP-1 expression in correlation with conventional clinicopathological parameters to clarify its prognostic significance in bladder cancer. In addition, the possible correlation of TSP-1 expression with microvessel count, VEGF expression, p53 expression as well as with the expression of the extracellular matrix components was studied to explore its implication in vascularization and tumour stroma remodeling. Methods: The immunohistochemical expression of TSP-1 in tumour cells and in the tumour stroma was studied in 148 formalin-fixed paraffin-embedded urothelial cell carcinoma tissue samples. Results: TSP-1 was detected in perivascular tissue, at the epithelial-stromal junction, in the stroma and in tumour cells in the majority of the cases. In tumour cells, low TSP-1 expression was observed in 43% of the cases, moderate and high in 7%, while 50% showed absence of TSP expression. A higher TSP-1 immunoreactivity in well and moderately differentiated tumours compared to poorly differentiated was noted. PT1 tumours showed decreased TSP-1 expression in comparison to pTa and pT2-4 tumours. Increased tumour cell TSP-1 expression was related to increased microvessel density. In the tumour stroma, 37% of the cases showed small amount of TSP-1 expression, 7.5% moderate and high, while 55% of the cases showed absence of TSP-1 stromal immunoreactivity. Stromal TSP-1 expression was inversely correlated with tumour stage and tumour size. This expression was also positively correlated with microvessel density, VEGF expression and extracellular matrix components tenascin and fibronectin. Using univariate and multivariate analysis we didn't find any significant correlation of TSP-1 expression in superficial tumours in both tumour cells and tumour stroma in terns of the risk of recurrence and disease progression. Conclusion: Our data suggest that both tumour and stromal TSP-1 expression may play a role in tumour aggressiveness and angiogenesis. In addition, the correlation of stromal TSP-1 expression with extracellular matrix components fibronectin and tenascin indicate its possible implication in tumour stroma remodeling. © 2006 Ioachim et al; licensee BioMed Central Ltd
Expression of matrix metalloproteinase-9 (gelatinase B) in benign, premalignant and malignant laryngeal lesions
The matrix metalloproteinases (MMPs) are a
family of proteolytic zinc-containing enzymes, which
are responsible for the breakdown of the extracellular
matrix components in pathological and physiological
conditions. They are involved in basement membrane
disruption, stroma and blood vessel penetration,
metastasis and more recently there is evidence that they
participate in tumor growth and angiogenic events.
Matrix metalloproteinase 2 and 9 (MMP 2 and 9) belong
to the gelatinases, a subgroup of MMPs, and have the
capacity to degrade the triple helix type IV collagen of
basal lamina of the basement membrane. With the
present study, we tried to demonstrate the expression of
MMP-9 immunohistochemically, comparatively in
benign, premalignant and malignant lesions of the
larynx. We studied 154 laryngeal lesions including 55
squamous cell carcinomas, 8 in situ carcinomas, 54 cases
of dysplasia (of low and intermediate grade), 13
papillomas and 24 cases of keratosis. Overexpression of
MMP 9 was observed in 74.4% and 50% in invasive and
in situ squamous cell carcinomas respectively. In
dysplastic cases, in papillomas and in keratoses the
percentage of overexpression was 62.9%, 61.53% and
54.16% respectively and the expression of MMP-9 was significantly higher in invasive squamous cell
carcinomas compared to dysplasias (p=0.000004). Also
significantly higher was the expression of MMP-9 in
dysplastic cases compared to papillomas (p=0.023). The
MMP-9 expression was related neither to survival nor to
the other available clinicopathological parameters
(tumor size, grade, clinical stage, lymph node status and
patient age). In conclusion, our study indicates that the
expression of MMP-9 is up-regulated in a stepwise
fashion, with two main steps, the first one, when a
dysplastic lesion evolves and the next one, when the
dysplasia progresses to invasive carcinoma
Thrombospondin-1 expression in breast cancer: prognostic significance and association with p53 alterations, tumour angiogenesis and extracellular matrix components
Thrombospondin (TSP-1) is a 450-kd adhesive glycoprotein that was initially discovered in platelets and subsequently in a variety of cell types. Several reports suggest that TSP-1 possesses tumour suppressor function, through its ability to inhibit tumour neovascularization. In this study we investigated tissue sections from 124 breast carcinomas for the immuno-histochemical expression of TSP-1 protein and its relationship to several clinicopathological parameters. The possible relationship to hormone receptors content, p53 protein, proliferation associated indices, angiogenesis, VEGF expression and extracellular matrix components (tenascin, fibronectin, laminin, collagen type IV and syndecan-1) was also estimated. TSP-1 was detected in the perivascular tissue, at the epithelial-stromal junction, in the stroma and in the tumour cells. High tumour cell TSP-1 expression was observed in 9.7%, moderate in 17.7%, mild in 10.5%, while 62.1% of the cases were negative for TSP-1 expression. The survival analysis showed an increased risk of recurrence associated with low TSP-1 tumour cell expression. High stromal TSP-1 expression was observed in 3.2% of the cases, moderate in 3.3%, mild in 27.4%, while 63.6% of the cases showed absence of TSP-1 expression. This expression was higher in invasive lobular type of breast cancer and inversely correlated with the lymph node involvement and the estrogen receptor content. Stromal TSP-1 expression was also positively correlated with extracellular matrix components expression, tenascin, fibronectin, collagen type IV, laminin, and syndecan-1. The relationship of TSP-1 expression with tumor angiogenesis, growth fraction and p53 protein expression was not significant. Our data suggest that TSP-1 expression seems to be associated with favorable biological behavior and may have clinical value in terms of predicting the risk of recurrence. In addition, TSP-1 might not be a direct anti-angiogenic factor, although it seems to be implicated in the remodeling of breast cancer tissue through interaction with other extracellular matrix component