Ovarian cancer is a relatively rare but highly lethal disease. Of all gynecologic malignancies, ovarian cancer is the second most common and the leading cause of death. The World Cancer Research Fund International says that about 239,000 new cases were diagnosed in 2012. The five-year survival rate for all stages of ovarian cancer is about 30-50%. The disease is generally advanced when diagnosed due to a lack of early signs. If ovarian cancer is found earlier, treatment works much better. However, the mechanism underlying the metastatic progression of ovarian cancer is largely unknown, impeding the development of drugs for advanced, relapsed disease.
A paper, published 12 December 2016 in the journal Oncogene, now provides a way to inhibit metastasis of ovarian cancer, a discovery that may improve patient prognosis. The researchers said "our studies support a key regulatory role for the fractalkine axis in advanced and relapsed peritoneal metastasis in epithelial ovarian carcinoma." The study is led by Maria Barbolina at the University of Illinois.
Barbolina's team has been studying epithelial ovarian carcinoma -- the most common type of ovarian cancer – for years. In a 2012 study published in Molecular Cancer Research, they analyzed human specimens and established cell lines, finding that the fractalkine receptor (or called CX3CR1) is expressed in primary and metastatic ovarian carcinoma cells. These cancer cells migrated toward the chemokine fractalkine (or called CX3CL1), which is an activating ligand of CX3CR1. In addition, blocking CX3CR1 significantly reduces cancer cell migration. These findings indicate that the CX3CL1/CX3CR1 signaling may contribute to the progression of ovarian cancer.
Chemokines are a family of small cytokine proteins produced by various cells, and they have the ability to induce chemotaxis, a process in which cells direct their movement according to the presence of chemicals in their environment. Chemokine receptors are molecules found on the surface of certain cells that interact with a chemokine. Studies have suggested chemokines as key regulators of carcinogenesis because they can shape the tumor microenvironment. Furthermore, expression of chemokines in human tumors is associated with poor prognosis.
In the present study, they continued investigating the role of the fractalkine axis in disease metastasis and its influence on patient prognosis. They demonstrated in mouse models that CX3CR1 indeed plays a role in metastasis of ovarian cancer. Additionally, downregulation of CX3CR1 lightens metastatic burden in the mice. CX3CL1 regulates organ-specific peritoneal colonization. The researchers also found that high levels of CX3CR1 associate with shorter survival. All together, the study demonstrates the role of the fractalkine axis in metastasis of epithelial ovarian carcinoma.
Many cancer drugs target G protein-coupled receptors, the largest family of cell-surface molecules involved in signal transmission. CX3CR1 is a member this receptor family. It may be reasonable to target CX3CR1 to inhibit ovarian cancer metastasis. By the way, if you need CX3CR1, CX3CL1 or other bio-molecules like Recombinant DSC2, Cusabio is a good supplier.
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