Dataset Information

The Crowded Crosstalk between Cancer Cells and Stromal Microenvironment in Gynecological Malignancies: Biological Pathways and Therapeutic Implication.

ABSTRACT: The tumor microenvironment plays a pillar role in the progression and the distance dissemination of cancer cells in the main malignancies affecting women-epithelial ovarian cancer, endometrial cancer and cervical cancer. Their milieu acquires specific properties thanks to intense crosstalk between stromal and cancer cells, leading to a vicious circle. Fibroblasts, pericytes, lymphocytes and tumor associated-macrophages orchestrate most of the biological pathways. In epithelial ovarian cancer, high rates of activated pericytes determine a poorer prognosis, defining a common signature promoting ovarian cancer proliferation, local invasion and distant spread. Mesenchymal cells also release chemokines and cytokines under hormonal influence, such as estrogens that drive most of the endometrial cancers. Interestingly, the architecture of the cervical cancer milieu is shaped by the synergy of high-risk Human Papilloma Virus oncoproteins and the activity of stromal estrogen receptor ?. Lymphocytes represent a shield against cancer cells but some cell subpopulation could lead to immunosuppression, tumor growth and dissemination. Cytotoxic tumor infiltrating lymphocytes can be eluded by over-adapted cancer cells in a scenario of immune-tolerance driven by T-regulatory cells. Therefore, the tumor microenvironment has a high translational potential offering many targets for biological and immunological therapies.

SUBMITTER: De Nola R

PROVIDER: S-EPMC6567055 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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The Crowded Crosstalk between Cancer Cells and Stromal Microenvironment in Gynecological Malignancies: Biological Pathways and Therapeutic Implication.

De Nola Rosalba R Menga Alessio A Castegna Alessandra A Loizzi Vera V Ranieri Girolamo G Ranieri Girolamo G Cicinelli Ettore E Cormio Gennaro G

International journal of molecular sciences 20190515 10

The tumor microenvironment plays a pillar role in the progression and the distance dissemination of cancer cells in the main malignancies affecting women-epithelial ovarian cancer, endometrial cancer and cervical cancer. Their <i>milieu</i> acquires specific properties thanks to intense crosstalk between stromal and cancer cells, leading to a vicious circle. Fibroblasts, pericytes, lymphocytes and tumor associated-macrophages orchestrate most of the biological pathways. In epithelial ovarian can ...[more]

PMID: 31096567

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Project description:Eicosanoids, bio-active lipid molecules, evoke a multitude of biological effects that directly affect cancer cells and indirectly affect tumor microenvironment. An emerging role has been shown for eicosanoids in the pathogenesis of gynecological malignancies which include cancers of the vulva, vagina, cervix, uterine, and ovary. Eicosanoid biosynthesis pathways start at the metabolism of phospholipids by phospholipase A2 then proceeding to one of three pathways: the cyclooxygenase (COX), lipoxygenase (LOX), or P450 epoxygenase pathways. The most studied eicosanoid pathways include COX and LOX; however, more evidence is appearing to support further study of the P450 epoxygenase pathway in gynecologic cancers. In this review, we present the current knowledge of the role of COX, LOX and P450 pathways in the pathogenesis of gynecologic malignancies. Vulvar and vaginal cancer, the rarest subtypes, there is association of COX-2 expression with poor disease specific survival in vulvar cancer and, in vaginal cancer, COX-2 expression has been found to play a role in mucosal inflammation leading to disease susceptibility and transmission. Cervical cancer is associated with COX-2 levels 7.4 times higher than in healthy tissues. Additionally, HPV elevates COX-2 levels through the EGFR pathway and HIV promotes elevated COX-2 levels in cervical tissue as well as increases PGE2 levels eliciting inflammation and progression of cancer. Evidence supports significant roles for both the LOX and COX pathways in uterine cancer. In endometrial cancer, there is increased expression of 5-LOX which is associated with adverse outcomes. Prostanoids in the COX pathway PGE2 and PGF2? have been shown to play a significant role in uterine cancer including alteration of proliferation, adhesion, migration, invasion, angiogenesis, and the inflammatory microenvironment. The most studied gynecological malignancy in regard to the potential role of eicosanoids in tumorigenesis is ovarian cancer in which all three pathways have shown to be associated or play a role in ovarian tumorigenesis directly on the tumor cell or through modulation of the tumor microenvironment. By identifying the gaps in knowledge, additional pathways and targets could be identified in order to obtain a better understanding of eicosanoid signaling in gynecological malignancies and identify potential new therapeutic approaches.

Dataset Information

The Crowded Crosstalk between Cancer Cells and Stromal Microenvironment in Gynecological Malignancies: Biological Pathways and Therapeutic Implication.

Publications

The Crowded Crosstalk between Cancer Cells and Stromal Microenvironment in Gynecological Malignancies: Biological Pathways and Therapeutic Implication.

Similar Datasets

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