Abstract
BackgroundPreviously some groups demonstrated that CD44 variant 6 (CD44v6) is correlated with progression and metastasis of ovarian cancer. However, a number of other groups failed to find such an association. Moreover, epithelial ovarian cancer is known to easily metastasize to distinct sites such as the pelvic and abdominal cavities, but the potential association of CD44v6 expression with site-specific metastasis of ovarian cancer has not been explored. This study sought to evaluate the expression of CD44 standard (CD44s) and CD44v6 in primary, metastatic and recurrent epithelial ovarian cancer to explore the potential association of CD44s and CD44v6 with tumor progression and recurrence.MethodsTumor specimens were procured from patients with advanced (FIGO III, G3) and recurrent ovarian serous adenocarcinoma. CD44s and CD44v6 expression in the tumor tissues was evaluated by real-time RT-PCR and Western blot. Moreover, serum soluble CD44s or CD44v6 concentrations of early stage (FIGO I, G1), advanced (FIGO III, G3) and recurrent ovarian serous adenocarcinoma patients were determined by enzyme-linked immunosorbent assays (ELISA). CD44v6 expression in a different set of tumor samples on an ovarian cancer tissue chip was evaluated by immunohistochemistry (IHC) and the correlation of CD44v6 expression with clinicopathologic features was analyzed. Finally, the effects of knockdown of CD44v6 in SKOV3 cells on cell adhesion, invasion and migration were assessed.ResultsThe expression of CD44v6, but not CD44s, is up-regulated in recurrent ovarian serous cancer compared to advanced primary tumor. CD44v6 expression is also preferentially increased in the tumor at the abdominal cavity metastasis site of advanced diseases. Consistently, serum soluble CD44v6 levels of recurrent ovarian cancer were higher than those of early stage and advanced primary diseases. The IHC data demonstrate that CD44v6 expression is correlated with clinicopathologic features and tumor progression. Lastly, knockdown of CD44v6 decreases the adhesion and migration but not invasion capacities of SKOV3 cells.ConclusionsCD44v6 expression levels are associated with epithelial ovarian cancer progression, metastasis and relapse. Moreover, serum soluble CD44v6 may be used as a potential marker for identifying tumor relapse. Finally, CD44v6 may play a role in ovarian cancer metastasis by mediating tumor cell adhesion and migration.
Highlights
Some groups demonstrated that CD44 standard (CD44s) variant 6 (CD44v6) is correlated with progression and metastasis of ovarian cancer
CD44 variant 6 (CD44v6) expression is preferentially increased in the tumor at the abdominal cavity metastasis site of advanced diseases
The IHC data demonstrate that CD44v6 expression is correlated with clinicopathologic features and tumor progression
Summary
Epithelial ovarian cancer is the most lethal gynecological ies generated conflicting data. Epithelial ovarian sion of CD44s and CD44v6 in primary, metastatic and cancer is characterized by frequent development of pel- recurrent epithelial ovarian cancer to explore the potenvic and abdominal cavity metastases in its asymptomatic tial association of CD44s and CD44v6 with tumor prostage [2]. R variant forms of CD44 (CD44v), in which an additional segment encoded by one or more of the variant exons is inserted in the extracellular domain of CD44s, which is. C ever, aberrant expression of CD44v has been implicated in the initiation, progression and recurrence of various hu-. E pancreatic adenocarcinoma cell line in animal models [23,24] Since these seminal studies, it has been established that CD44v6 plays role in tumor develop-. Rment and progression in a variety of human cancers gression and recurrence
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