Next Article in Journal
Cyclophilin A in Arrhythmogenic Cardiomyopathy Cardiac Remodeling
Previous Article in Journal
In Vitro Study of the Anticancer Effects of Biotechnological Extracts of the Endangered Plant Species Satureja Khuzistanica
Article Menu

Export Article

Open AccessReview

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

1
Department of Tissues and Organs Transplantation and Cellular Therapies, D.E.O.T., University of Bari “Aldo Moro”, Piazza G. Cesare, 11-Policlinico 70124 Bari, Italy
2
Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari “Aldo Moro”, Via E. Orabona, 4, 70125 Bari, Italy
3
Department of Biomedical and Human Oncological Science, 2nd Unit of Obstetrics and Gynecology, University of Bari “Aldo Moro”, Piazza G. Cesare, 11-Policlinico 70124 Bari, Italy
4
Interventional Oncology Unit with Integrate Section of Translational Medical Oncology, IRCCS, Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy
5
Gynaecologic Oncology Unit, IRCCS, Istituto Tumori Giovanni Paolo II, 70142 Bari, Italy
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(10), 2401; https://doi.org/10.3390/ijms20102401
Received: 17 April 2019 / Revised: 12 May 2019 / Accepted: 13 May 2019 / Published: 15 May 2019
  |  
PDF [1699 KB, uploaded 15 May 2019]
  |  

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 α. 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. View Full-Text
Keywords: pericytes; fibroblasts; tumor-associated macrophages; lymphocytes; estrogens; Human Papilloma Virus; ovarian cancer; endometrial cancer; cervical cancer pericytes; fibroblasts; tumor-associated macrophages; lymphocytes; estrogens; Human Papilloma Virus; ovarian cancer; endometrial cancer; cervical cancer
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

De Nola, R.; Menga, A.; Castegna, A.; Loizzi, V.; Ranieri, G.; Cicinelli, E.; Cormio, G. The Crowded Crosstalk between Cancer Cells and Stromal Microenvironment in Gynecological Malignancies: Biological Pathways and Therapeutic Implication. Int. J. Mol. Sci. 2019, 20, 2401.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top