BACKGROUND: Cancer of the pancreas is the fourth leading cause of cancer death in industrialized countries. In malignancy, actively proliferating cells may be effectively targeted and killed by anti-cancer therapies, ...BACKGROUND: Cancer of the pancreas is the fourth leading cause of cancer death in industrialized countries. In malignancy, actively proliferating cells may be effectively targeted and killed by anti-cancer therapies, but stem cells may survive and support re-growth of the tumor. Thus, new strategies for the treatment of cancer clearly will also have to target cancer stem cells. The goal of the present study was to determine whether pancreatic carcinoma cell growth may be driven by a subpopulation of cancer stem cells. Because previous data implicated ABCG2 and CD133 as stem cell markers in hematopoietic and neural stem/progenitor cells, we analyzed the expression of these two proteins in pancreatic carcinoma cell lines. METHODS: Five established pancreatic adenocarcinoma cell lines were analyzed. Total RNA was isolated and real- time RT-PCR was performed to determine the expression of ABCG2 and CD133. Surface expression of ABCG2 and CD133 was analyzed by flow cytometric analysis. RESULTS: All pancreatic carcinoma cell lines tested expressed significantly higher levels of ABCG2 than non-malignant fibroblasts or two other malignant non- pancreatic cell lines, i.e., SaOS2 osteosarcoma and SKOV3 ovarian cancer. Elevated CD133 expression was found in two out of five pancreatic carcinoma cell lines tested. Using flow cytometric analysis we confirmed surface expression of ABCG2 in all five lines. Yet, CD133 surface expression was detectable in the two cell lines, A818-6 and PancTu1, which exhibited higher mRNA levels.CONCLUSIONS: Two stem cell markers, ABCG2 and CD133 are expressed in pancreatic carcinoma cell lines. ABCG2 and/or CD133 positive cells may represent subpopulation of putative cancer stem cells also in this malignancy. Because cancer stem cells are thought to be responsible for tumor initiation and its recurrence after an initial response to chemotherapy, they may be a very promising target for new drug developments.展开更多
Cancer stem cells(CSCs) are a small subpopulation in cancer, have been proposed to be cancer-initiating cells, and have been shown to be responsible for chemotherapy resistance and cancer recurrence. The identificatio...Cancer stem cells(CSCs) are a small subpopulation in cancer, have been proposed to be cancer-initiating cells, and have been shown to be responsible for chemotherapy resistance and cancer recurrence. The identification of CSC subpopulations inside a tumor presents a new understanding of cancer development because it implies that tumors can only be eradicated by targeting CSCs. Although advances in liver cancer detection and treatment have increased the possibility of curing the disease at early stages, unfortunately, most patients will relapse and succumb to their disease. Strategies aimed at efficiently targeting liver CSCs are becoming important for monitoring the progress of liver cancer therapy and for evaluating new therapeutic approaches. Herein, we provide a critical discussion of biological markers described in the literature regarding liver cancer stem cells and the potential of these markers to serve as therapeutic targets.展开更多
Cancer stem cells (CSCs) or tumor initiating cells are rare cells that are able to establish a tumor or metastasis. Identification of those CSCs is, however, cumbersome even in established cell lines. Several cancer s...Cancer stem cells (CSCs) or tumor initiating cells are rare cells that are able to establish a tumor or metastasis. Identification of those CSCs is, however, cumbersome even in established cell lines. Several cancer stem cell markers were reported to be expressed by ovarian cancer. Those cancer stem cells are gifted with lower vulnerability to irradiation and cytostatic drugs explaining the high incidence of recurrence after treatment. A variety of different cancer stem cell markers were described for epithelial tumors. Also, cancer cell lines were assessed for stem cell markers with no common denominator. The expression of CD24, CD44, CD117, CD133, ABCG2, ALDH was determined for cells from 22 patients. Ovarian cancer cells were collected from ascites. Part of the tumor cells were analyzed immediately and stained for the above mentioned cancer stem cell markers. The remainder of the cells was cultured for several weeks using standard stem cell culture conditions. We observed a large variety in expression of putative stem cell markers for primary tumors. After two weeks of culture spheres were seen in several cultures, indicative for cancer stem cells, though not all patients’ cells were able to form spheres. Our data show for the first time the heterogeneity in marker display in primary tumors. Also for the cultured cells stem cell markers were determined. None of the stem cell markers was expressed by all patients’ cells. No correlation with tumor type was demonstrated. The complexity of expression challenges the isolation of cancer stem展开更多
BACKGROUND SOX2 is a regulator of pluripotent cellular transcription, yet it has been recently integrated in cancer biology. The present study provides an analytic insight into the correlation of SOX2 overexpression w...BACKGROUND SOX2 is a regulator of pluripotent cellular transcription, yet it has been recently integrated in cancer biology. The present study provides an analytic insight into the correlation of SOX2 overexpression with cancer metastasis and patient survival. AIM To investigate the association of SOX2 overexpression with metastasis and its implication in the prognosis of cancer patients. METHODS A meta-analysis was conducted including studies that compared the association of low or high SOX2 expression with lymph node metastasis (LNM) and/or distant metastasis (DM). The following data were additionally extracted: survival, including the overall survival (OS) and disease-free survival (DFS), and prevalence of high and low SOX2 expression. Odds ratios (commonly known as ORs) and their respective 95% confidence intervals (CIs) were used to investigate the association between SOX2 expression and LNM and DM, while hazard ratios (commonly known as HRs) and 95%CIs were applied to evaluate the prognostic markers. RESULTS In a total of 2643 patients (60.88% males), the pooled prevalence of SOX2 overexpression was 46.22%(95%CI: 39.07%-53.38%) in different types of cancer. SOX2 overexpression significantly correlated with DM (OR = 1.79, 95%CI: 1.20- 3.25, P < 0.008) compared to low SOX2 expression. In subgroups analyses, a high SOX2 expression was associated with LNM in cancers of the lung, breast, and colon and associated with DM in hepatic, head and neck, and colon cancers. SOX2 overexpression was also associated with a shorter OS (HR = 1.65, 95%CI:1.34-2.04, P < 0.001) and DFS (HR = 1.54, 95%CI: 1.14-2.08, P = 0.005). CONCLUSION A remarkable role of SOX2 overexpression was observed in cancer biology and metastasis. However, many questions in the regulatory pathways need to be addressed to reveal as many functional aspects as possible to tailor new targeted therapeutic strategies.展开更多
文摘BACKGROUND: Cancer of the pancreas is the fourth leading cause of cancer death in industrialized countries. In malignancy, actively proliferating cells may be effectively targeted and killed by anti-cancer therapies, but stem cells may survive and support re-growth of the tumor. Thus, new strategies for the treatment of cancer clearly will also have to target cancer stem cells. The goal of the present study was to determine whether pancreatic carcinoma cell growth may be driven by a subpopulation of cancer stem cells. Because previous data implicated ABCG2 and CD133 as stem cell markers in hematopoietic and neural stem/progenitor cells, we analyzed the expression of these two proteins in pancreatic carcinoma cell lines. METHODS: Five established pancreatic adenocarcinoma cell lines were analyzed. Total RNA was isolated and real- time RT-PCR was performed to determine the expression of ABCG2 and CD133. Surface expression of ABCG2 and CD133 was analyzed by flow cytometric analysis. RESULTS: All pancreatic carcinoma cell lines tested expressed significantly higher levels of ABCG2 than non-malignant fibroblasts or two other malignant non- pancreatic cell lines, i.e., SaOS2 osteosarcoma and SKOV3 ovarian cancer. Elevated CD133 expression was found in two out of five pancreatic carcinoma cell lines tested. Using flow cytometric analysis we confirmed surface expression of ABCG2 in all five lines. Yet, CD133 surface expression was detectable in the two cell lines, A818-6 and PancTu1, which exhibited higher mRNA levels.CONCLUSIONS: Two stem cell markers, ABCG2 and CD133 are expressed in pancreatic carcinoma cell lines. ABCG2 and/or CD133 positive cells may represent subpopulation of putative cancer stem cells also in this malignancy. Because cancer stem cells are thought to be responsible for tumor initiation and its recurrence after an initial response to chemotherapy, they may be a very promising target for new drug developments.
基金Supported by The Natural National Science Foundation of ChinaNo.11272365
文摘Cancer stem cells(CSCs) are a small subpopulation in cancer, have been proposed to be cancer-initiating cells, and have been shown to be responsible for chemotherapy resistance and cancer recurrence. The identification of CSC subpopulations inside a tumor presents a new understanding of cancer development because it implies that tumors can only be eradicated by targeting CSCs. Although advances in liver cancer detection and treatment have increased the possibility of curing the disease at early stages, unfortunately, most patients will relapse and succumb to their disease. Strategies aimed at efficiently targeting liver CSCs are becoming important for monitoring the progress of liver cancer therapy and for evaluating new therapeutic approaches. Herein, we provide a critical discussion of biological markers described in the literature regarding liver cancer stem cells and the potential of these markers to serve as therapeutic targets.
文摘Cancer stem cells (CSCs) or tumor initiating cells are rare cells that are able to establish a tumor or metastasis. Identification of those CSCs is, however, cumbersome even in established cell lines. Several cancer stem cell markers were reported to be expressed by ovarian cancer. Those cancer stem cells are gifted with lower vulnerability to irradiation and cytostatic drugs explaining the high incidence of recurrence after treatment. A variety of different cancer stem cell markers were described for epithelial tumors. Also, cancer cell lines were assessed for stem cell markers with no common denominator. The expression of CD24, CD44, CD117, CD133, ABCG2, ALDH was determined for cells from 22 patients. Ovarian cancer cells were collected from ascites. Part of the tumor cells were analyzed immediately and stained for the above mentioned cancer stem cell markers. The remainder of the cells was cultured for several weeks using standard stem cell culture conditions. We observed a large variety in expression of putative stem cell markers for primary tumors. After two weeks of culture spheres were seen in several cultures, indicative for cancer stem cells, though not all patients’ cells were able to form spheres. Our data show for the first time the heterogeneity in marker display in primary tumors. Also for the cultured cells stem cell markers were determined. None of the stem cell markers was expressed by all patients’ cells. No correlation with tumor type was demonstrated. The complexity of expression challenges the isolation of cancer stem
文摘BACKGROUND SOX2 is a regulator of pluripotent cellular transcription, yet it has been recently integrated in cancer biology. The present study provides an analytic insight into the correlation of SOX2 overexpression with cancer metastasis and patient survival. AIM To investigate the association of SOX2 overexpression with metastasis and its implication in the prognosis of cancer patients. METHODS A meta-analysis was conducted including studies that compared the association of low or high SOX2 expression with lymph node metastasis (LNM) and/or distant metastasis (DM). The following data were additionally extracted: survival, including the overall survival (OS) and disease-free survival (DFS), and prevalence of high and low SOX2 expression. Odds ratios (commonly known as ORs) and their respective 95% confidence intervals (CIs) were used to investigate the association between SOX2 expression and LNM and DM, while hazard ratios (commonly known as HRs) and 95%CIs were applied to evaluate the prognostic markers. RESULTS In a total of 2643 patients (60.88% males), the pooled prevalence of SOX2 overexpression was 46.22%(95%CI: 39.07%-53.38%) in different types of cancer. SOX2 overexpression significantly correlated with DM (OR = 1.79, 95%CI: 1.20- 3.25, P < 0.008) compared to low SOX2 expression. In subgroups analyses, a high SOX2 expression was associated with LNM in cancers of the lung, breast, and colon and associated with DM in hepatic, head and neck, and colon cancers. SOX2 overexpression was also associated with a shorter OS (HR = 1.65, 95%CI:1.34-2.04, P < 0.001) and DFS (HR = 1.54, 95%CI: 1.14-2.08, P = 0.005). CONCLUSION A remarkable role of SOX2 overexpression was observed in cancer biology and metastasis. However, many questions in the regulatory pathways need to be addressed to reveal as many functional aspects as possible to tailor new targeted therapeutic strategies.
