Dataset Information

Epithelial cell adhesion molecule (EpCAM) is involved in prostate cancer chemotherapy/radiotherapy response in vivo.

ABSTRACT:

Background

Development of chemo-/radioresistance is a major challenge for the current prostate cancer (CaP) therapy. We have previously demonstrated that epithelial cell adhesion molecule (EpCAM) is associated with CaP growth and therapeutic resistance in vitro, however, the role of EpCAM in CaP in vivo is not fully elucidated. Here, we aimed to investigate how expression of EpCAM is involved in CaP growth and chemo-/radiotherapy response in NOD/SCID mouse models in vivo and to validate its role as a therapeutic target for CaP therapy.

Methods

EpCAM was knocked down in PC-3 CaP cell line using short hairpin RNA (shRNA). The effect of EpCAM-knockdown (KD) on tumour growth, chemo-/radiotherapy response and animal survival was evaluated on subcutaneous (s.c) and orthotopic mouse models.

Results

We found that KD of EpCAM significantly inhibited tumour growth, increased xenograft sensitivity to chemotherapy/radiotherapy, and prolonged the survival of tumour-bearing mice. In addition, we demonstrated that KD of EpCAM is associated with downregulation of the PI3K/Akt/mTOR pathway.

Conclusions

In conclusion, our data confirms that CaP growth and chemo-/radioresistance in vivo is associated with over-expression of EpCAM, which serves both a functional biomarker and promising therapeutic target.

SUBMITTER: Ni J

PROVIDER: S-EPMC6233586 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

Epithelial cell adhesion molecule (EpCAM) is involved in prostate cancer chemotherapy/radiotherapy response in vivo.

Ni Jie J Cozzi Paul P Beretov Julia J Duan Wei W Bucci Joseph J Graham Peter P Li Yong Y

BMC cancer 20181112 1

<h4>Background</h4>Development of chemo-/radioresistance is a major challenge for the current prostate cancer (CaP) therapy. We have previously demonstrated that epithelial cell adhesion molecule (EpCAM) is associated with CaP growth and therapeutic resistance in vitro, however, the role of EpCAM in CaP in vivo is not fully elucidated. Here, we aimed to investigate how expression of EpCAM is involved in CaP growth and chemo-/radiotherapy response in NOD/SCID mouse models in vivo and to validate ...[more]

PMID: 30419852

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Project description:ObjectivesThe epithelial cell adhesion molecule (EpCAM) is one of the most commonly used markers of cancer stem cells (CSCs), but the clinical and prognostic significance of EpCAM in gastric cancer (GC) remains disputable. Motivated by heterogeneous and inconclusive results, we conducted a systematic review and meta-analysis to systematically summarize and elucidate the association between EpCAM overexpression and GC patients.MethodsThe PubMed, Cochrane Library, Medline, Web of Knowledge and the China National Knowledge Infrastructure (CNKI) databases were searched to identify relevant studies. The RevMan 5.3 software was used for the meta-analysis. Fixed-effects or random-effects models were applied depending on the presence of heterogeneity. The pooled odds ratio (ORs) and 95% confidence intervals (CIs) were applied to estimate the associations between EpCAM and gastric cancer. For the significant heterogeneity studies, sensitivity analyses were applied based on the population to test the robustness of the pooled results and identify possible sources of heterogeneity.ResultsA total of 11 studies including 1960 GC patients met our inclusion criteria. The results of the meta-analyses revealed that there were significant differences in EpCAM overexpression and tumour size (OR = 2.97, 95% CI: 2.13~4.13, P < 0.00001), the nature of the tissue (OR = 80.30, 95% CI: 29.21~220.81, P < 0.00001), lymph node metastasis (OR = 2.78, 95% CI: 1.23~6.27, P = 0.01), and the cumulative 5-year overall survival rate (OR = 0.54, 95% CI:0.29~0.99, P = 0.05). No significant associations were identified between EpCAM overexpression and gender (OR = 0.89, 95% CI: 0.66~1.19, P = 0.43), age (OR = 1.13, 95% CI: 0.58~2.20, P = 0.73), tumour stage (OR = 2.26, 95% CI: 0.79~6.45, P = 0.13), distant metastasis (OR = 2.15, 95% CI: 0.20~22.69, P = 0.52), TNM stage (OR = 5.14, 95% CI: 0.77~34.37, P = 0.09), Lauren type (OR = 1.18, 95% CI: 0.08~16.45, P = 0.9), differentiation (OR = 1.88, 95% CI: 0.65~5.41, P = 0.24). However, due to significant heterogeneity in tumor stage, lymph node metastasis, TNM stage, differentiation and Lauren type, these results should be taken carefully.ConclusionsThe meta-analysis demonstrated that the expression of EpCAM in the gastric cancer group was greater than that in the control group. Moreover, EpCAM overexpression was associated with larger tumour size, lymphnode metastasis and worse prognosis in gastric cancer. Due to significant heterogeneity, the sensitivity analysis suggests that population factor may be an important source of heterogeneity, and these results should be treated with caution. EpCAM may be useful as a novel prognostic factor, and large-scale and well-designed studies are needed to validate our results in the future.

Dataset Information

Epithelial cell adhesion molecule (EpCAM) is involved in prostate cancer chemotherapy/radiotherapy response in vivo.

Background

Methods

Results

Conclusions

Publications

Epithelial cell adhesion molecule (EpCAM) is involved in prostate cancer chemotherapy/radiotherapy response in vivo.

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