Examination of the Fractalkine and Fractalkine Receptor Expression in Fallopian Adenocarcinoma Reveals Differences When Compared to Ovarian Carcinoma

Abstract

Fallopian adenocarcinoma is a rare malignancy arising in the epithelium of the fallopian tube. Fallopian tube epithelium has been proposed as a tissue origin for high-grade serous ovarian carcinoma, the deadliest gynecologic malignancy. Given the commonalities in dissemination and treatment of these malignancies, we contemplated the possibility of similar patterns of gene expression underlying their progression. To reveal potential similarities or differences in the gene expression of fallopian adenocarcinoma and high-grade serous ovarian carcinoma, we tested expression of the fractalkine receptor (CX3CR1) and its ligand, fractalkine (CX3CL1), in the specimens of normal and pathologic fallopian tube using immunohistochemistry. Our data show that CX3CR1 is expressed in the normal, cancer adjacent normal, inflammatory, and malignant fallopian epithelium. CX3CL1 was expressed only by the normal and cancer adjacent normal fallopian tube epithelium; its expression was largely lost in the inflammatory and malignant fallopian epithelium. In opposite, both CX3CR1 and CX3CL1 are expressed in high-grade serous ovarian carcinoma. These findings are consistent with an idea that fallopian adenocarcinoma and high-grade serous ovarian carcinoma, although currently thought to arise from the same organ, may not share similar molecular characteristics.

CD44 Regulates Formation of Spheroids and Controls Organ-Specific Metastatic Colonization in Epithelial Ovarian Carcinoma

“…IHC staining was performed as described before (24)(25)(26)(27). Antigen retrieval was achieved through incubation at 95 C for 15 minutes in sodium citrate buffer, pH 6.0.…”

Emergent role of the fractalkine axis in dissemination of peritoneal metastasis from epithelial ovarian carcinoma

“…Targeted therapies directed against tumor-specific pathways and molecules have been more successful in treating metastasis compared to the conventional cytotoxic chemotherapy ( 18 ). We reasoned that the chemokine family G protein-coupled receptor fractalkine (CX 3 CR1) might be such a molecule, because it is expressed in 64% of metastatic ovarian carcinoma specimens ( 19 ) and in vitro studies showed that CX 3 CR1-positive ovarian carcinoma cells adhered to mesothelial monolayer and proliferated in CX 3 CL1-dependent manner ( 19 , 20 ); moreover, we previously reported that CX 3 CR1 was expressed in all tested types of stromal and epithelial ovarian carcinoma ( 19 , 21 , 22 ). Chemokine receptors are seven transmembrane G protein-coupled receptors (GPCR) that are activated upon ligand (chemokine) binding resulting in activation of intracellular signaling networks that regulate processes vital for both normal and cancer cells ( 23 – 25 ).…”

Chemokine expression in patients with ovarian cancer or benign ovarian tumors

“…The membrane-anchored form mediates strong cell adhesion while soluble form acts mainly as chemoattractant for T cells, NK cells, dendritic cells and CD14 positive monocytes [ [5][6][7]. CX3CL1 is a specific ligand of the CX3CR1 receptor [ 8 ]. The expression of CX3CL1 and CX3CR1 has been established in different cancers such as breast, prostate, pancreatic and ovarian cancer [ [9][10][11][12][13] ].…”

“…The available data on CX3CL1 involvement in ovarian tumors are extremely limited. Published papers have reported that specimens of both ovarian carcinoma and benign tumors expressed CX3CL1 and its receptor [ 7 , 8 , 13 ]. However, no data on the serum level of this chemokine in patients suffering from ovarian cancer or benign ovarian tumors have been reported.…”