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Review
. 2024 Mar 12;13(6):495.
doi: 10.3390/cells13060495.

Diversity of Intercellular Communication Modes: A Cancer Biology Perspective

Thanzeela Ebrahim  1 , Abdul Shukkur Ebrahim  2 , Mustapha Kandouz  1   3
Affiliations
Review

Diversity of Intercellular Communication Modes: A Cancer Biology Perspective

Thanzeela Ebrahim et al. Cells. .

Abstract

From the moment a cell is on the path to malignant transformation, its interaction with other cells from the microenvironment becomes altered. The flow of molecular information is at the heart of the cellular and systemic fate in tumors, and various processes participate in conveying key molecular information from or to certain cancer cells. For instance, the loss of tight junction molecules is part of the signal sent to cancer cells so that they are no longer bound to the primary tumors and are thus free to travel and metastasize. Upon the targeting of a single cell by a therapeutic drug, gap junctions are able to communicate death information to by-standing cells. The discovery of the importance of novel modes of cell-cell communication such as different types of extracellular vesicles or tunneling nanotubes is changing the way scientists look at these processes. However, are they all actively involved in different contexts at the same time or are they recruited to fulfill specific tasks? What does the multiplicity of modes mean for the overall progression of the disease? Here, we extend an open invitation to think about the overall significance of these questions, rather than engage in an elusive attempt at a systematic repertory of the mechanisms at play.

Keywords: adherens junction; apoptotic bodies; bystander effect; cancer; desmosome; eph; ephrin; exosome; extracellular vesicle; gap junction; intercellular communication; tight junction; tunelling nanotube.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Summary of membrane-based modes of intercellular communication. AJ: Adherens Junction. GJ: Gap Junction. TJ: Tight Junction. DSM: Desmosome. EV: Extracellular Vesicle. AB: Apoptotic Body. TNT: Tunneling Nanotube. Cx: Connexin. See text for details.
Figure 2
Figure 2
Range of action of different modes of intercellular communication. While various short-range junctions such as TJs and AJs, and junction-less Eph/ephrin proteins involve tight contacts, GJs are able, thanks to the “bystander effect” (BE), to transfer cytotoxic signals to multiple cells within few surrounding layers. Tunneling nanotubes (TNTs) and extracellular vesicles (EVs) extend this range of action significantly.
Figure 3
Figure 3
Cell–cell and cell–extracellular matrix (ECM) mechanical communication. Intercellular communication not only generates mechanical tensions, by interacting with the cytoskeleton, it is also responsive to endogenous mechanical forces as well as physical features of the ECM. See text for details.
Figure 4
Figure 4
Cell–cell communication contributes to the immune responses, including anti-tumor immunity. Anti-tumor immunological defense mechanisms, including antigen (Ag) presentation, involve multiple modes of intercellular communication. (a) Gap junctions (GJs) transfer antigenic viral peptides from infected cells into noninfected neighbors, resulting in the recognition and targeting by cytotoxic T lymphocyte (CTL). (b) GJs allow Ag transfer from cancer cells to dendritic cells (DCs), which is presented to T Cells, as part of an anti-tumor immune response. GJs also transfer antigenic peptides between tumor cells and endothelial cells, resulting in the latter’s recognition and elimination by cytotoxic T lymphocytes. (c) In apoptotic tumor cells, GJs transfer antigens generated by caspase cleavage, from apoptotic cells to DCs, to be presented to T Cells, thus activating an antitumor immune response. Similarly, apoptotic bodies derived from apoptotic mycobacteria-infected macrophages contain mycobacteria-derived antigens which are transferred to DCs and presented to T Cells.
Figure 5
Figure 5
Interplay between various modes of cell–cell communication. Intercellular communication can be mediated by multiple modes at the same time, in a collaborative or antagonistic manner, depending on the context. (a) Junctional communication modes tight junctions (TJs) and adherens junctions (AJs) are structurally and functionally related and form a junctional complex. This “junctional nexus” interacts also with gap junctions (GJs). (b) Junctional proteins such as connexins or claudins, as well as Eph/ephrin proteins are transported remotely by extracellular vesicles (EVs), whose functions they contribute to. (c) Functional GJs are present in the ends of some TNTs and contribute to electrical coupling.
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