Mast cells, angiogenesis and lymphangiogenesis in human gastric cancer

Giuseppe Sammarco, Gilda Varricchi, Valentina Ferraro, Michele Ammendola, Michele De Fazio, Donato Francesco Altomare, Maria Luposella, Lorenza Maltese, Giuseppe Currò, Gianni Marone, Girolamo Ranieri, Riccardo Memeo

Research output: Contribution to journalArticlepeer-review

Abstract

Gastric cancer is diagnosed in nearly one million new patients each year and it remains the second leading cause of cancer-related deaths worldwide. Although gastric cancer represents a heterogeneous group of diseases, chronic inflammation has been shown to play a role in tumorigenesis. Cancer development is a multistep process characterized by genetic and epigenetic alterations during tumour initiation and progression. The stromal microenvironment is important in maintaining normal tissue homeostasis or promoting tumour development. A plethora of immune cells (i.e., lymphocytes, macrophages, mast cells, monocytes, myeloid-derived suppressor cells, Treg cells, dendritic cells, neutrophils, eosinophils, natural killer (NK) and natural killer T (NKT) cells) are components of gastric cancer microenvironment. Mast cell density is increased in gastric cancer and there is a correlation with angiogenesis, the number of metastatic lymph nodes and the survival of these patients. Mast cells exert a protumorigenic role in gastric cancer through the release of angiogenic (VEGF-A, CXCL8, MMP-9) and lymphangiogenic factors (VEGF-C and VEGF-F). Gastric mast cells express the programmed death ligands (PD-L1 and PD-L2) which are relevant as immune checkpoints in cancer. Several clinical undergoing trials targeting immune checkpoints could be an innovative therapeutic strategy in gastric cancer. Elucidation of the role of subsets of mast cells in different human gastric cancers will demand studies of increasing complexity beyond those assessing merely mast cell density and microlocalization.

Original languageEnglish
Article numberE2106
JournalInternational Journal of Molecular Sciences
Volume20
Issue number9
DOIs
Publication statusPublished - May 1 2019

Keywords

  • Angiogenesis
  • Cancer
  • Gastric cancer
  • Immune cells
  • Inflammation
  • Lymphangiogenesis
  • Mast cells

ASJC Scopus subject areas

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

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