Interleukin‐8 (IL‐8), as an inflammatory chemokine, has been previously shown to contribute to tumorigenesis in several malignancies including the ovarian cancer. However, little is known about how IL‐8 promotes the metastasis and invasion of ovarian cancers cells. In this study, we found that IL‐8 and its receptors CXCR1 and CXCR2 were up‐regulated in advanced ovarian serous cancer tissues. Furthermore, the level of IL‐8 and its receptors CXCR1 and CXCR2 expression were associated with ovarian cancer stage, grade and lymph node metastasis. In vitro, IL‐8 promoted ovarian cancer cell migration, initiated the epithelial‐mesenchymal transition (EMT) program and activated Wnt/β‐catenin signalling. However, when treated with Reparixin (inhibitor of both IL‐8 receptors CXCR1 and CXCR2), effect of both endogenous and exogenous IL‐8 was reversed. Together, our results indicated that IL‐8 triggered ovarian cancer cells migration partly through Wnt/β‐catenin pathway mediated EMT, and IL‐8 may be an important molecule in the invasion and metastasis of ovarian cancer.
Pelvic organ prolapse (POP) is a common symptom of pelvic floor disorders which is characterized by the descent of the uterus, bladder or bowel from their normal anatomical position towards or through the vagina. Among the older population, the incidence of POP increases with age. It is becoming necessary to recognize that POP is a degenerative disease that is correlated with age. In recent years, studies have been performed to improve understanding of the cellular and molecular mechanisms concerning senescent fibroblasts in pelvic tissues, which contribute to the loss of structure supporting the pelvic organs. These mechanisms can be classified into gene and mitochondrial dysfunctions, intrinsic senescence processes, protein imbalance and alterations in stem cells. The present review provides an integrated overview of the current research and concepts regarding POP, in addition to discussing how fibroblasts can be targeted to evade the negative impact of senescence on POP. However, it is probable that other mechanisms that can also cause POP exist during cell senescence, which necessitates further research and provides new directions in the development of novel medical treatment, stem cell therapy and non‑surgical interventions for POP.
Epithelial-mesenchymal transition (EMT) is a biological process that is associated with cancer metastasis and invasion. In cancer, EMT promotes cell motility, invasion and distant metastasis. Interleukin (IL)-8 is highly expressed in tumors and may induce EMT. The IL‑8/IL‑8R axis has a vital role in EMT in carcinoma, which is regulated by several signaling pathways, including the transforming growth factor β‑spleen associated tyrosine kinase/Src-AKT/extracellular signal‑regulated kinase, p38/Jun N‑terminal kinase‑activating transcription factor‑2, phosphoinositide 3-kinase/AKT, nuclear factor-κB and Wnt signaling pathways. Blocking the IL‑8/IL‑8R signaling pathway may be a novel strategy to reduce metastasis and improve patient survival rates. This review will cover IL‑8‑IL‑8R signaling pathway in tumor epithelial-mesenchymal transition.
Introduction: In the pathology of pelvic organ prolapse (POP), little is known about the contributing role of pelvic microenvironment. Also, the age-related differences in pelvic microenvironment of POP patients is always ignored. In the present study, we investigated the age-related differences in pelvic microenvironment between Young POP patients and Old POP patients, and the novel cell types and critical regulators which contributes to the age-related differences.Methods: Single-cell transcriptomic analyses were used to detect the changes in cell composition and gene expression from the pelvic microenvironment of control group (<60 years), Young POP group (60 years). Then, immunohistochemistry and immunofluorescence were used to verify the novel cell types and critical regulators in the pelvic microenvironment. Furthermore, histopathological alteration and mechanical property alteration in POP with different ages were revealed by vaginal tissue histology and biomechanical testing.Results: The up-regulated biological process in Old women with POP is mainly related to chronic inflammation, while the up-regulated biological process in Young women with POP is mainly related to extracellular matrix metabolism. Meantime, CSF3+ endothelial cells and FOLR2+ macrophages were found to play a central role in inducing pelvic chronic inflammation. Furthermore, the collagen fiber and mechanical property of POP patients decreased with aging.Conclusions: Taken together, this work provides a valuable resource for deciphering the aging-related immune cell types and the critical regulators in pelvic microenvironment. With better understanding of normal and abnormal events in this pelvic microenvironment, we provided rationales of personalized medicine for POP patients with different ages.