The expression of Duffy antigen receptor for chemokines by epithelial ovarian cancer decreases growth potential

Abstract

Epithelial ovarian cancer (EOC) is one of the main causes of cancer-associated mortality in females with gynecological malignancies. Duffy antigen receptor for chemokines (DARC) has previously been reported to be involved in tumor growth and the inhibition of tumor metastasis. However, the association between DARC and EOC remains unknown. The aim of the present study was to investigate the expression of DARC in the SKOV3 human epithelial ovarian cancer cell line with the establishment of a subcutaneous model in nude mice. To investigate the effects of DARC on the tumorigenesis of human epithelial ovarian cancer cells, GV287-DARC-L.V lentiviral vectors containing a DARC overexpression construct were transfected into SKOV3 cells. The present study revealed that transfection with DARC reduced the viability of SKOV3 cells in vitro by performing an MTT assay. SKOV3-DARC and SKOV3-negative control (NC) cells cultured in vitro were injected into nude mice to establish a subcutaneous model. The ovarian tumor volumes and the tumor weights were observed. Immunohistochemistry to detect CD31 expression was used to determine the microvessel density (MVD) in SKOV3-DARC and SKOV3-NC tumors. The results of the present study revealed that DARC-induced inhibition of tumor growth was associated with MVD in xenograft tumors. This suggested that DARC was a negative regulator of tumor growth in EOC, primarily via the inhibition of tumor angiogenesis.

Beyond Cell Motility: The Expanding Roles of Chemokines and Their Receptors in Malignancy

“…Indeed, ACKR1 was strongly connected to improved outcomes in breast cancer as well as in several other malignancies, at times upon co-expression with ACKR2 or ACKR4 (188)(189)(190)(191)(192). Accordingly, ACKR1 was causatively linked to reduced tumor growth and metastasis in animal models, and ACKR1 single nucleotide polymorphisms that were related to chemokine sequestration affected angiogenesis, tumorigenesis and lung metastasis (193)(194)(195). The anti-tumor activities of ACKR1 were mediated not only by reducing microvessel density, but also by inhibiting atypical cancer-related activities, such as MMP9 production and tumor cell proliferation, as well as increasing tumor cell senescence (192,(194)(195)(196); from the mechanistic perspective, it was demonstrated that ACKR1 caused anti-tumor effects by interfering with CXCR2-induced STAT3 activation in pancreatic adenocarcinoma cells (192).…”

“…Accordingly, ACKR1 was causatively linked to reduced tumor growth and metastasis in animal models, and ACKR1 single nucleotide polymorphisms that were related to chemokine sequestration affected angiogenesis, tumorigenesis and lung metastasis (193)(194)(195). The anti-tumor activities of ACKR1 were mediated not only by reducing microvessel density, but also by inhibiting atypical cancer-related activities, such as MMP9 production and tumor cell proliferation, as well as increasing tumor cell senescence (192,(194)(195)(196); from the mechanistic perspective, it was demonstrated that ACKR1 caused anti-tumor effects by interfering with CXCR2-induced STAT3 activation in pancreatic adenocarcinoma cells (192). Moreover, in prostate cancer ACKR1 expressed by vascular endothelial cells interacted with tetraspanin KAI1 (CD82) on tumor cells, leading to decreased DNA synthesis and induction of tumor cell senescence (195); in parallel, it was found that melanomaexpressed KAI interacted with endothelial cell-expressed ACKR1 preventing CXCL8-inudced gap formation in endothelial cells and leading to tumor cell senescence (197).…”

Effect of functional genetic variants in chemokine decoy receptors on the recurrence risk of breast cancer

“…Recently, studies highlight that DARC plays a potential role in malignancy, the most essential of which is served as a inhibit barrier of metastases . Studies increasingly discovered the association between clinical outcomes and DARC: Necrosis and decreased metastases were induced by DARC in lung cancer; the absence of DARC expression in prostate cancer tended to poor survival; and the expression of DARC by epithelial ovarian cancer decreases growth potential . Multiple reports showed that downregulation of CCBP2 in transformed cells was consistent with tumor progression and oncogene activation in Kaposi sarcoma .…”

Construction of ultrasonic nanobubbles carrying CAIX polypeptides to target carcinoma cells derived from various organs

“…Next, horseradish peroxidase-labeled goat anti-rabbit secondary antibody (Beyotime Institute of Biotechnology) was added, and the sections were incubated at 37 °C for 1 h. After in the presence of DAB reagent and counterstaining cell nuclei with hematoxylin, the sections were mounted and examined under an optical microscope. Microvessel density (MVD) was determined from five random fields (at × 200 magnification) of each section, and only tumor blood vessels with vascular lumen or linear vascular shape were used for MVD analysis [ 25 ].…”