The Effect of Cancer Cell-Derived Exosomal Proteins on Macrophage
Polarization: An In-depth Review
Abstract
Background: Cancer is characterized by unregulated cell
proliferation, enabling it to invade and spread to different organs and
tissues in the body. Cancer progression is intricately influenced by the
complex dynamics within the tumor microenvironment (TME). The tumor
microenvironment (TME) is a composite and dynamic network comprising
cancer cells and various immune cells, including tumor-associated
macrophages. Exosomes facilitate the cross-talk between different cancer
cells and other cells. This review particularly focuses on exosomal
proteins derived from different cancer cells in mounting the complex
communication between cancer cells and macrophages within the tumor
microenvironment. Most cancer-derived exosomal proteins polarize
macrophages towards M2 phenotype, promoting cancer aggressiveness, while
a few have role switching towards the M1 phenotype, inhibiting cancer
proliferation, respectively. In this review, we summarize, for the first
time, the dual impact of cancer cell-derived exosomal proteins on
macrophage polarization and the associated signaling pathways, offering
valuable insights for developing innovative therapeutic strategies
against diverse cancer types. Conclusion: The exosomal proteins
derived from different cancer cells can polarize macrophages into either
classically activated M1 phenotype or alternatively activated M2
phenotype. This review provides insights and describes the role of
different cancer cell-derived exosomal proteins and the associated
signaling pathways that lead to macrophage polarization and further
promote or inhibit cancer progression.