Molecular Dynamics of Trogocytosis and Other Contact-Dependent Cell Trafficking Mechanisms in Tumor Pathogenesis

TL;DR

This paper reviews how cancer cells use contact-dependent methods to exchange materials with neighboring cells, aiding tumor growth and survival.

Contribution

The paper highlights four underappreciated contact-dependent trafficking mechanisms in tumor pathogenesis.

Findings

Tumor cells use trogocytosis, entosis, cell fusion, and tunneling nanotubes to transfer materials.

These mechanisms help cancer cells evade immunity and create a supportive tumor microenvironment.

Filamentous actin synthesis is a conserved driver of these trafficking processes.

Abstract

During oncogenesis, cancer cells must develop complex strategies to proliferate, survive, and avoid the body’s natural defenses. One class of strategies tumor cells can use is contact-dependent transfers of cellular materials. This review highlights four important mechanisms by which cancer cells exchange and obtain cellular components from their neighbors. These processes can result in increased metastatic capacity, better evasion of immune detection, drug resistance, genomic instability, and dysregulated metabolism.

Horizontal trafficking of subcellular components, such as nucleic acids, proteins, and membrane fragments, is utilized by tumor cells to facilitate tumor cell proliferation and survival. Conventionally, tumor cells have been known to undergo long-range transfer through the import and export of extracellular vesicles and exosomes. However, other means of intercellular transfer are also employed by tumor cells. These trafficking methods can facilitate changes in anti-tumor immunity and distribute oncogenic protein variants to nearby cells to provide a hospitable tumor microenvironment. The molecular mechanisms that drive many of these cell trafficking mechanisms are conserved, relying on de novo synthesis of filamentous actin. However, the delineation between these processes is not yet known. This review will highlight four recently characterized and underappreciated contact-dependent intercellular trafficking mechanisms: (i) trogocytosis, (ii) entosis, (iii) cell fusion, and (iv) tunneling nanotubes/microtubes utilized by tumor cells to promote a hospitable microenvironment.

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