Roles of cell fusion between mesenchymal stromal/stem cells and malignant cells in tumor growth and metastasis

FEBS J. 2021 Mar;288(5):1447-1456. doi: 10.1111/febs.15483. Epub 2020 Jul 24.

Abstract

Invasion and metastasis are the basic characteristics and important markers of malignant tumors, which are also the main cause of death in cancer patients. Epithelial-mesenchymal transition (EMT) is recognized as the first step of tumor invasion and metastasis. Many studies have demonstrated that cell fusion is a common phenomenon and plays a critical role in cancer development and progression. At present, cancer stem cell fusion has been considered as a new mechanism of cancer metastasis. Mesenchymal stromal/stem cell (MSC) is a kind of adult stem cells with high self-renewal ability and multidifferentiation potential, which is used as a very promising fusogenic candidate in the tumor microenvironment and has a crucial role in cancer progression. Many research results have shown that MSCs are involved in the regulation of tumor growth and metastasis through cell fusion. However, the role of cell fusion between MSCs and malignant cells in tumor growth and metastasis is still controversial. Several studies have demonstrated that MSCs can enhance malignant characteristics, promoting tumor growth and metastasis by fusing with malignant cells, while other conflicting reports believe that MSCs can reduce tumorigenicity upon fusion with malignant cells. In this review, we summarize the recent research on cell fusion events between MSCs and malignant cells in tumor growth and metastasis. The elucidation of the molecular mechanisms between MSC fusion and tumor metastasis may provide an effective strategy for tumor biotherapy.

Keywords: cancer stem/initiating cells; cell fusion; epithelial-mesenchymal transition; mesenchymal stromal/stem cells; tumor metastasis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Communication
  • Cell Fusion*
  • Cell Line, Tumor
  • Cell Movement
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Matrix Metalloproteinase 9 / genetics*
  • Matrix Metalloproteinase 9 / metabolism
  • Mesenchymal Stem Cells / metabolism*
  • Mesenchymal Stem Cells / pathology
  • Neoplasm Metastasis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Signal Transduction
  • Tumor Microenvironment / genetics

Substances

  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • MMP9 protein, human
  • Matrix Metalloproteinase 9