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Up-regulation of CD44 in the development of metastasis, recurrence and drug resistance of ovarian cancer.

Gao Y, Foster R, Yang X, Feng Y, Shen JK, Mankin HJ, Hornicek FJ, Amiji MM, Duan Z - Oncotarget (2015)

Bottom Line: A significant association has been shown between CD44 expression and both the disease free survival and overall survival.A strong increase of CD44 was found in the tumor recurrence of mouse model.Finally, when CD44 was knocked down, proliferation, migration/invasion activity, and spheroid formation were significantly suppressed, while drug sensitivity was enhanced.

View Article: PubMed Central - PubMed

Affiliation: Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

ABSTRACT
The clinical significance of Cluster of Differentiation 44 (CD44) remains controversial in human ovarian cancer. The aim of this study is to evaluate the clinical significance of CD44 expression by using a unique tissue microarray, and then to determine the biological functions of CD44 in ovarian cancer. In this study, a unique ovarian cancer tissue microarray (TMA) was constructed with paired primary, metastatic, and recurrent tumor tissues from 26 individual patients. CD44 expression in TMA was assessed by immunohistochemistry. Both the metastatic and recurrent ovarian cancer tissues expressed higher level of CD44 than the patient-matched primary tumor. A significant association has been shown between CD44 expression and both the disease free survival and overall survival. A strong increase of CD44 was found in the tumor recurrence of mouse model. Finally, when CD44 was knocked down, proliferation, migration/invasion activity, and spheroid formation were significantly suppressed, while drug sensitivity was enhanced. Thus, up-regulation of CD44 represents a crucial event in the development of metastasis, recurrence, and drug resistance to current treatments in ovarian cancer. Developing strategies to target CD44 may prevent metastasis, recurrence, and drug resistance in ovarian cancer.

No MeSH data available.


Related in: MedlinePlus

Knockdown of CD44 by lentiviral shRNA increased the paclitaxel sensitivity of ovarian cancer cellsPanel (A) status of OVCAR8, OVCAR8Lentivirus only, OVCAR8Non-specific shRNA, and OVCAR8CD44 shRNA cells that differed between representative concentrations of paclitaxel (0 μM and 0.006 μM). Panel (B) MTT assay showing cell viability of the above mention four cell lines with different concentrations of paclitaxel. The MTT assay was conducted in triplicate.
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Figure 4: Knockdown of CD44 by lentiviral shRNA increased the paclitaxel sensitivity of ovarian cancer cellsPanel (A) status of OVCAR8, OVCAR8Lentivirus only, OVCAR8Non-specific shRNA, and OVCAR8CD44 shRNA cells that differed between representative concentrations of paclitaxel (0 μM and 0.006 μM). Panel (B) MTT assay showing cell viability of the above mention four cell lines with different concentrations of paclitaxel. The MTT assay was conducted in triplicate.

Mentions: To examine whether repression of CD44 levels would increase the drug sensitivity of ovarian cancer cells, the MTT assay was performed on the established cell lines OVCAR8Lentivirus only, OVCAR8Non-specific shRNA, and OVCAR8CD44 shRNA after incubating with paclitaxel. OVCAR8 cells without any treatment were used as the control. The representative pictures of different cells dosed with 0 μM paclitaxel and 0.006 μM paclitaxel were shown in Figure 4 Panel A. The results showed minimal survival of OVCAR8CD44 shRNA in medium containing 0.006 μM paclitaxel, while a substantial number of OVCAR8, OVCAR8Lentivirus only, and OVCAR8Non-specific shRNA cells were still able to tolerate this level of paclitaxel exposure. Further analysis of the MTT data indicated that knockdown of CD44 significantly restored the sensitivity to chemotherapeutic drug paclitaxel in OVCAR8 (Figure 4 Panel B).


Up-regulation of CD44 in the development of metastasis, recurrence and drug resistance of ovarian cancer.

Gao Y, Foster R, Yang X, Feng Y, Shen JK, Mankin HJ, Hornicek FJ, Amiji MM, Duan Z - Oncotarget (2015)

Knockdown of CD44 by lentiviral shRNA increased the paclitaxel sensitivity of ovarian cancer cellsPanel (A) status of OVCAR8, OVCAR8Lentivirus only, OVCAR8Non-specific shRNA, and OVCAR8CD44 shRNA cells that differed between representative concentrations of paclitaxel (0 μM and 0.006 μM). Panel (B) MTT assay showing cell viability of the above mention four cell lines with different concentrations of paclitaxel. The MTT assay was conducted in triplicate.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496219&req=5

Figure 4: Knockdown of CD44 by lentiviral shRNA increased the paclitaxel sensitivity of ovarian cancer cellsPanel (A) status of OVCAR8, OVCAR8Lentivirus only, OVCAR8Non-specific shRNA, and OVCAR8CD44 shRNA cells that differed between representative concentrations of paclitaxel (0 μM and 0.006 μM). Panel (B) MTT assay showing cell viability of the above mention four cell lines with different concentrations of paclitaxel. The MTT assay was conducted in triplicate.
Mentions: To examine whether repression of CD44 levels would increase the drug sensitivity of ovarian cancer cells, the MTT assay was performed on the established cell lines OVCAR8Lentivirus only, OVCAR8Non-specific shRNA, and OVCAR8CD44 shRNA after incubating with paclitaxel. OVCAR8 cells without any treatment were used as the control. The representative pictures of different cells dosed with 0 μM paclitaxel and 0.006 μM paclitaxel were shown in Figure 4 Panel A. The results showed minimal survival of OVCAR8CD44 shRNA in medium containing 0.006 μM paclitaxel, while a substantial number of OVCAR8, OVCAR8Lentivirus only, and OVCAR8Non-specific shRNA cells were still able to tolerate this level of paclitaxel exposure. Further analysis of the MTT data indicated that knockdown of CD44 significantly restored the sensitivity to chemotherapeutic drug paclitaxel in OVCAR8 (Figure 4 Panel B).

Bottom Line: A significant association has been shown between CD44 expression and both the disease free survival and overall survival.A strong increase of CD44 was found in the tumor recurrence of mouse model.Finally, when CD44 was knocked down, proliferation, migration/invasion activity, and spheroid formation were significantly suppressed, while drug sensitivity was enhanced.

View Article: PubMed Central - PubMed

Affiliation: Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

ABSTRACT
The clinical significance of Cluster of Differentiation 44 (CD44) remains controversial in human ovarian cancer. The aim of this study is to evaluate the clinical significance of CD44 expression by using a unique tissue microarray, and then to determine the biological functions of CD44 in ovarian cancer. In this study, a unique ovarian cancer tissue microarray (TMA) was constructed with paired primary, metastatic, and recurrent tumor tissues from 26 individual patients. CD44 expression in TMA was assessed by immunohistochemistry. Both the metastatic and recurrent ovarian cancer tissues expressed higher level of CD44 than the patient-matched primary tumor. A significant association has been shown between CD44 expression and both the disease free survival and overall survival. A strong increase of CD44 was found in the tumor recurrence of mouse model. Finally, when CD44 was knocked down, proliferation, migration/invasion activity, and spheroid formation were significantly suppressed, while drug sensitivity was enhanced. Thus, up-regulation of CD44 represents a crucial event in the development of metastasis, recurrence, and drug resistance to current treatments in ovarian cancer. Developing strategies to target CD44 may prevent metastasis, recurrence, and drug resistance in ovarian cancer.

No MeSH data available.


Related in: MedlinePlus