Role of tumor microenvironment in ovarian cancer pathobiology

Ghoneum, Alia; Afify, Hesham; Salih, Ziyan; Kelly, Michael G.; Said, Neveen

doi:10.18632/oncotarget.25126

Cited by 55 publications

(45 citation statements)

References 161 publications

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“…This function of CCL14 plays an important anticancer role in OC, since a study demonstrated that there are a large number of macrophages and T lymphocytes in the OC microenvironment (44). Other studies reported that in OC, macrophages and T lymphocytes upregulate the expression levels of CCR1 and CCR5 receptors, which creates an antitumor immune environment leading to the necrosis of OC cells (45,46). Furthermore, another study investigating multiple myeloma demonstrated that when CCL14 binds to CCR1 and CCR5, it can lead to chemoattraction and recruitment of macrophages, which promotes proliferation by activating the PI3K-AKT, MAPK/ERK, JNK and p38MAPK pathways (42).…”

Section: Discussionmentioning

confidence: 99%

C‑C motif chemokine 14 as a novel potential biomarker for predicting the prognosis of epithelial ovarian cancer

et al. 2020

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Previous studies have demonstrated that CC motif chemokine 14 (CCL14) plays an important role in the occurrence and development of cancer. However, the significance of CCL14 in the progression and prognosis of epithelial ovarian cancer (EOC) has not yet been reported. The standard EnVision procedure for tissue microarrays was used to evaluate the immunohistochemical expression of CCL14 protein in 154 patients with EOC who underwent tumor-debulking operations at the Central Cancer Department of Sun Yat-Sen University (Guangzhou, China) or Jiangmen Central Hospital (Jiangmen, China). The association between CCL14 expression and clinicopathological variables was assessed using the χ 2 test. For survival status of patients with EOC, Kaplan-Meier survival analysis and a Cox multivariate regression model was used. Expression of CCL14 protein was significantly associated with International Federation of Gynecology and Obstetric stage (P=0.014) and pN status(P=0.005). Kaplan-Meier survival analysis revealed that the survival time of patients with high expression of CCL14 was 136.1 months and that of patients with low expression of CCL14 was 98.9 months (P=0.026). Multivariate analysis demonstrated that CCL14 upregulation was associated with overall survival time (HR, 0.48; 95% CI, 0.261-0.896; P=0.021) and progression-free survival time (HR,0.437; 95% CI, 0.228-0.839; P=0.013). In conclusion, CCL14 is an independent prognostic factor for EOC and upregulation of CCL14 is associated with a more favorable prognosis in patients with EOC.

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Section: Discussionmentioning

confidence: 99%

C‑C motif chemokine 14 as a novel potential biomarker for predicting the prognosis of epithelial ovarian cancer

et al. 2020

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“…In this process, polarized epithelial cells change their phenotype to motile mesenchymal cells. The downregulation of epithelial markers, such as E-cadherin, is replaced by the upregulation of mesenchymal markers such as vimentin, Slug, Snail, fibronectin, zinc-finger E-box binding homeobox 1 (ZEB1), ZEB2, and α-smooth muscle actin, allowing cells to migrate and invade [ 61 , 66 , 67 ]. These changes correlate with metastasis, recurrence, chemoresistant tumors, and poor outcome.…”

Section: Multifaceted Nature Of Macrophages In the Tmementioning

confidence: 99%

Regulation of Ovarian Cancer Prognosis by Immune Cells in the Tumor Microenvironment

Drakes

Stiff

2018

Cancers

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It is estimated that in the United States in 2018 there will be 22,240 new cases of ovarian cancer and 14,070 deaths due to this malignancy. The most common subgroup of this disease is high-grade serous ovarian cancer (HGSOC), which is known for its aggressiveness, high recurrence rate, metastasis to other sites, and the development of resistance to conventional therapy. It is important to understand the ovarian cancer tumor microenvironment (TME) from the viewpoint of the function of pre-existing immune cells, as immunocompetent cells are crucial to mounting robust antitumor responses to prevent visible tumor lesions, disease progression, or recurrence. Networks consisting of innate and adaptive immune cells, metabolic pathways, intracellular signaling molecules, and a vast array of soluble factors, shape the pathogenic nature of the TME and are useful prognostic indicators of responses to conventional therapy and immunotherapy, and subsequent survival rates. This review highlights key immune cells and soluble molecules in the TME of ovarian cancer, which are important in the development of effective antitumor immunity, as well as those that impair effector T cell activity. A more insightful knowledge of the HGSOC TME will reveal potential immune biomarkers to aid in the early detection of this disease, as well as biomarkers that may be targeted to advance the design of novel therapies that induce potent antitumor immunity and survival benefit.

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“…Ovarian cancer is the fifth leading cause of cancer-related deaths in women in the United States, and has a low survival rate, due in part to the frequent late stage at diagnosis [1,2]. Despite aggressive surgical debulking and first-line platinum-based therapy, a~70% relapse rate is observed, attributable to chemoresistance and peritoneal metastasis [1].…”

Section: Introductionmentioning

confidence: 99%

Carcinoma-Associated Mesenchymal Stem Cells Promote Chemoresistance in Ovarian Cancer Stem Cells via PDGF Signaling

Raghavan

Snyder

Wang

et al. 2020

Cancers

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Within the ovarian cancer tumor microenvironment, cancer stem-like cells (CSC) interact with carcinoma associated mesenchymal stem/stromal cells (CA-MSC) through multiple secreted cytokines and growth factors. These paracrine interactions have been revealed to cause enrichment of CSC and their chemoprotection; however, it is still not known if platelet-derived growth factor (PDGF) signaling is involved in facilitating these responses. In order to probe this undiscovered bidirectional communication, we created a model of ovarian malignant ascites in the three-dimensional (3D) hanging drop heterospheroid array, with CSC and CA-MSC. We hypothesized that PDGF secretion by CA-MSC increases self-renewal, migration, epithelial to mesenchymal transition (EMT) and chemoresistance in ovarian CSC. Our results indicate that PDGF signaling in the CSC-MSC heterospheroids significantly increased stemness, metastatic potential and chemoresistance of CSC. Knockdown of PDGFB in MSC resulted in abrogation of these phenotypes in the heterospheroids. Our studies also reveal a cross-talk between PDGF and Hedgehog signaling in ovarian cancer. Overall, our data suggest that when the stromal signaling via PDGF to ovarian CSC is blocked in addition to chemotherapy pressure, the tumor cells are significantly more sensitive to chemotherapy. Our results emphasize the importance of disrupting the signals from the microenvironment to the tumor cells, in order to improve response rates. These findings may lead to the development of combination therapies targeting stromal signaling (such as PDGF and Hedgehog) that can abrogate the tumorigenic, metastatic and platinum resistant phenotypes of ovarian CSC through additional investigations.

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Role of tumor microenvironment in ovarian cancer pathobiology

Cited by 55 publications

References 161 publications

C‑C motif chemokine 14 as a novel potential biomarker for predicting the prognosis of epithelial ovarian cancer

C‑C motif chemokine 14 as a novel potential biomarker for predicting the prognosis of epithelial ovarian cancer

Regulation of Ovarian Cancer Prognosis by Immune Cells in the Tumor Microenvironment

Carcinoma-Associated Mesenchymal Stem Cells Promote Chemoresistance in Ovarian Cancer Stem Cells via PDGF Signaling

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