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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

CD44 is overexpressed in drug resistant ovarian cancer cell lines, along with the appearance of tumor recurrence in ovarian cancer xenograft modelsPanel (A and B) relative expression levels of CD44 and Pgp in drug resistant cell lines SKOV-3TR, OVCAR8TR, and parental sensitive cell lines SKOV-3, OVCAR8 were determined by western blot. The assay was conducted in triplicate. Panel (C) schematic of human ovarian cancer xenograft establishment and paclitaxel treatment, each group has six female nude mice. Panel (D) relative CD44 protein levels in tumors of human ovarian cancer xenograft model treated with different doses of paclitaxel evaluated by western blot, which was performed in triplicate. Panel (E) a semi-quantitative analysis of relative CD44 protein expression determined by western bolt.
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Figure 2: CD44 is overexpressed in drug resistant ovarian cancer cell lines, along with the appearance of tumor recurrence in ovarian cancer xenograft modelsPanel (A and B) relative expression levels of CD44 and Pgp in drug resistant cell lines SKOV-3TR, OVCAR8TR, and parental sensitive cell lines SKOV-3, OVCAR8 were determined by western blot. The assay was conducted in triplicate. Panel (C) schematic of human ovarian cancer xenograft establishment and paclitaxel treatment, each group has six female nude mice. Panel (D) relative CD44 protein levels in tumors of human ovarian cancer xenograft model treated with different doses of paclitaxel evaluated by western blot, which was performed in triplicate. Panel (E) a semi-quantitative analysis of relative CD44 protein expression determined by western bolt.

Mentions: Late-stage ovarian cancer exhibits more aggressive tumor progression, especially resistant to conventional chemotherapeutic drugs. Based on the results of CD44 immunostaining in our TMA, we further examined the relative expression levels of CD44 in two pairs of well-characterized drug sensitive and resistant ovarian cancer cell lines-SKOV-3/SKOV-3TR and OVCAR8/OVCAR8TR. The western blot results demonstrated that only SKOV-3TR and OVCAR8TR exhibited strong expression of P-glycoprotein (Pgp), however both the drug sensitive and drug resistant cell lines presented a ubiquitous level of CD44 expression. Moreover, SKOV-3TR and OVCAR8TR expressed significantly higher levels of CD44 than parental sensitive cell lines (Figure 2 Panel A and 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)

CD44 is overexpressed in drug resistant ovarian cancer cell lines, along with the appearance of tumor recurrence in ovarian cancer xenograft modelsPanel (A and B) relative expression levels of CD44 and Pgp in drug resistant cell lines SKOV-3TR, OVCAR8TR, and parental sensitive cell lines SKOV-3, OVCAR8 were determined by western blot. The assay was conducted in triplicate. Panel (C) schematic of human ovarian cancer xenograft establishment and paclitaxel treatment, each group has six female nude mice. Panel (D) relative CD44 protein levels in tumors of human ovarian cancer xenograft model treated with different doses of paclitaxel evaluated by western blot, which was performed in triplicate. Panel (E) a semi-quantitative analysis of relative CD44 protein expression determined by western bolt.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: CD44 is overexpressed in drug resistant ovarian cancer cell lines, along with the appearance of tumor recurrence in ovarian cancer xenograft modelsPanel (A and B) relative expression levels of CD44 and Pgp in drug resistant cell lines SKOV-3TR, OVCAR8TR, and parental sensitive cell lines SKOV-3, OVCAR8 were determined by western blot. The assay was conducted in triplicate. Panel (C) schematic of human ovarian cancer xenograft establishment and paclitaxel treatment, each group has six female nude mice. Panel (D) relative CD44 protein levels in tumors of human ovarian cancer xenograft model treated with different doses of paclitaxel evaluated by western blot, which was performed in triplicate. Panel (E) a semi-quantitative analysis of relative CD44 protein expression determined by western bolt.
Mentions: Late-stage ovarian cancer exhibits more aggressive tumor progression, especially resistant to conventional chemotherapeutic drugs. Based on the results of CD44 immunostaining in our TMA, we further examined the relative expression levels of CD44 in two pairs of well-characterized drug sensitive and resistant ovarian cancer cell lines-SKOV-3/SKOV-3TR and OVCAR8/OVCAR8TR. The western blot results demonstrated that only SKOV-3TR and OVCAR8TR exhibited strong expression of P-glycoprotein (Pgp), however both the drug sensitive and drug resistant cell lines presented a ubiquitous level of CD44 expression. Moreover, SKOV-3TR and OVCAR8TR expressed significantly higher levels of CD44 than parental sensitive cell lines (Figure 2 Panel A and 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