Fractalkine Receptor CX3CR1 Is Expressed in Epithelial Ovarian Carcinoma Cells and Required for Motility and Adhesion to Peritoneal Mesothelial Cells

Abstract

Epithelial ovarian carcinoma is a deadly disease, and little is known about the mechanisms underlying its metastatic progression. Using human specimens and established cell lines, we determined that the G protein-coupled seven-transmembrane fractalkine receptor (CX3CR1) is expressed in primary and metastatic ovarian carcinoma cells. Ovarian carcinoma cells robustly migrated toward CX3CL1, a specific ligand of CX3CR1, in a CX3CR1-dependent manner. Silencing of CX3CR1 reduced migration toward human ovarian carcinoma ascites fluid by approximately 70%. Importantly, adhesion of ovarian carcinoma cells to human peritoneal mesothelial cells was dependent on CX3CL1/CX3CR1 signaling. In addition, CX3CL1 was able to induce cellular proliferation. Together, our data suggest that the fractalkine network may function as a major contributor to the progression of epithelial ovarian carcinoma, and further attention to its role in the metastasis of this deadly malignancy is warranted.

Cystatin D Locates in the Nucleus at Sites of Active Transcription and Modulates Gene and Protein Expression

“…One of these genes is CX3CL1/fractalkine, which encodes a chemokine with pro-inflammatory and pro-tumorigenic activity in several types of cancer (29)(30)(31). The repressive effect of cystatin D on the secretion of CX3CL1/fractalkine in our system supports a tumor suppressive action.…”

Mechanisms and Targets Involved in Dissemination of Ovarian Cancer

“…Lymphotactin receptor XC chemokine receptor 1 (XCR1), a GPCR expressed in ovarian cancer and not in normal ovarian tissue, was shown to mediate increased migration and proliferation of ovarian cancer cells by interactions with lymphotactins 1 and 2 (132). Interaction of peritoneal cellexpressed membrane-bound form of fractalkine receptor C-X3-C motif ligand 1 (CX3CL1) with CX3C chemokine receptor 1 (CX3CR1) on ovarian tumor cells as a mediator of homing-related adhesion was demonstrated by impairment of adhesion with function blocking antibodies directed against CX3CL1 and also by its down-regulation by RNAi (133). The contribution of stromal cells to homing of disseminated ovarian cancer cells has also been investigated.…”

Fractalkine receptor is expressed in mature ovarian teratomas and required for epidermal lineage differentiation

“…According to our previous observations CX 3 CR1 was expressed in cells comprising ovarian teratoma tissue specimens [8], although the number of specimens was very limited in order to be able to draw any conclusions. In the present study we aimed to expand this observation on a larger number of ovarian teratoma specimens and determine the predominant cell type(s) positive for CX 3 CR1.…”

“…This procedure was performed as previously described [8,14,15] Antibodies were used at the following dilutions: 1:500 mouse anti-human-CK14 or CK18, or CX 3 CL1, rabbit anti-human CX 3 CR1 (Abcam ab8020) and 1:200 mouse anti-human-β-tubulin or goat anti-human actin in 3% BSA in a solution of 50 mM tris-buffered saline, pH 7.4, 150 mM NaCl, and 0.05% Tween-20 (TBST). Immunoreactive bands were visualized with anti-(mouse-IgG)-peroxidase, anti-(goat-IgG)-peroxidase, and anti-(rabbit-IgG)-peroxidase (Sigma, St. Louis, MO) (1:1000 in 3% BSA in TBST), and enhanced chemiluminescence was read using Chemidoc (Bio-Rad) and Bio-Rad Chemidoc ImageReader software.…”

“…Our previous data obtained using a limited number of subjects suggested that a chemokine receptor fractalkine (CX 3 CR1) is expressed in ovarian teratomas [8]. CX 3 CR1 is a G protein-coupled receptor with multiple functions in both the normal state and disease [9,10].…”