The crowded crosstalk between cancer cells and stromal microenvironment in gynecological malignancies: Biological pathways and therapeutic implication

Rosalba De Nola, Alessio Menga, Alessandra Castegna, Vera Loizzi, Girolamo Ranieri, Ettore Cicinelli, Gennaro Cormio

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish
Article numberE2401
JournalInternational Journal of Molecular Sciences
Volume20
Issue number10
DOIs
Publication statusPublished - May 2 2019

Keywords

  • Cervical cancer
  • Endometrial cancer
  • Estrogens
  • Fibroblasts
  • Human Papilloma Virus
  • Lymphocytes
  • Ovarian cancer
  • Pericytes
  • Tumor-associated macrophages

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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