Jie Zhu1,2, Ya Zheng1,2, Haiyan Zhang1,2, Yanmei Liu1,2, Hong Sun1,2, Pengnan Zhang1,2. 1. Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University Shanghai 200011, China. 2. Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Shanghai 200011, China.
Abstract
BACKGROUND: It has been reported that Galectin-1 (Gal-1) indicates bad prognosis of patients with ovarian cancer, and Gal-1 overexpression promotes metastasis of ovarian cancer cells. Nevertheless, the underlying mechanisms of the Gal-1-mediated enhancement of metastasis are still unclear. Furthermore, little is known about whether Gal-1 affects epithelial-mesenchymal transition (EMT) in ovarian cancer. METHODS: The human SKOV3-ip and SKOV3 cell lines were transfected with Gal-1 siRNAs and LV-Gal-1 lentivirus, respectively. Cell migration and cell invasion abilities were examined by transwell assays. Protein or mRNA levels of Gal-1, p-JNK1/2, t-JNK1/2, p-p38, t-p38 and EMT markers were detected via immunohistochemistry, qRT-PCR and western blot in SKOV3-ip as well as SKOV3 cells. A xenograft tumour model was used in vivo to ascertain whether upregulation of Gal-1 in ovarian cancer cells can enhance metastasis in vivo. RESULTS: In a total of 107 human ovarian cancer tissues, higher Gal-1 expression strongly associated with higher histological grade, more lymph node metastases and more advanced FIGO stage, while lower E-cadherin expression strongly associated with higher histological grade, more lymph node metastases and more advanced FIGO stage. In vitro assays revealed that Gal-1 promoted migration and invasion of ovarian cancer cells, as well as EMT. Additionally, the results showed that Gal-1 enhanced EMT, migration and invasion by activating the MAPK JNK/p38 signalling pathway. Moreover, in vivo bioluminescence imaging revealed that Gal-1 modulated ovarian cancer metastasis in nude mice. Immunochemistry of xenograft tumour tissues confirmed that Gal-1 may modulate metastasis and EMT via the MAPK JNK/p38 signalling pathway. Additionally, treatment of Gal-1 mice with the MAPK JNK/p38 signalling pathway antagonists SB203580 or SP600125 reduced cancer metastasis. CONCLUSION: Gal-1 enhances metastasis and EMT of ovarian cancer cells via promoting the activation of the MAPK JNK/p38 signalling pathway, suggesting the possibility that Gal-1 is a molecular target to prevent and cure ovarian cancer metastasis.
BACKGROUND: It has been reported that Galectin-1 (Gal-1) indicates bad prognosis of patients with ovarian cancer, and Gal-1 overexpression promotes metastasis of ovarian cancer cells. Nevertheless, the underlying mechanisms of the Gal-1-mediated enhancement of metastasis are still unclear. Furthermore, little is known about whether Gal-1 affects epithelial-mesenchymal transition (EMT) in ovarian cancer. METHODS: The human SKOV3-ip and SKOV3 cell lines were transfected with Gal-1 siRNAs and LV-Gal-1 lentivirus, respectively. Cell migration and cell invasion abilities were examined by transwell assays. Protein or mRNA levels of Gal-1, p-JNK1/2, t-JNK1/2, p-p38, t-p38 and EMT markers were detected via immunohistochemistry, qRT-PCR and western blot in SKOV3-ip as well as SKOV3 cells. A xenograft tumour model was used in vivo to ascertain whether upregulation of Gal-1 in ovarian cancer cells can enhance metastasis in vivo. RESULTS: In a total of 107 humanovarian cancer tissues, higher Gal-1 expression strongly associated with higher histological grade, more lymph node metastases and more advanced FIGO stage, while lower E-cadherin expression strongly associated with higher histological grade, more lymph node metastases and more advanced FIGO stage. In vitro assays revealed that Gal-1 promoted migration and invasion of ovarian cancer cells, as well as EMT. Additionally, the results showed that Gal-1 enhanced EMT, migration and invasion by activating the MAPK JNK/p38 signalling pathway. Moreover, in vivo bioluminescence imaging revealed that Gal-1 modulated ovarian cancer metastasis in nude mice. Immunochemistry of xenograft tumour tissues confirmed that Gal-1 may modulate metastasis and EMT via the MAPK JNK/p38 signalling pathway. Additionally, treatment of Gal-1mice with the MAPK JNK/p38 signalling pathway antagonists SB203580 or SP600125 reduced cancer metastasis. CONCLUSION:Gal-1 enhances metastasis and EMT of ovarian cancer cells via promoting the activation of the MAPK JNK/p38 signalling pathway, suggesting the possibility that Gal-1 is a molecular target to prevent and cure ovarian cancer metastasis.