Are Synapse-Like Structures a Possible Way for Crosstalk of Cancer with Its Microenvironment?

Abstract

The failure of therapies directed at targets within cancer cells highlight the necessity for a paradigm change in cancer therapy. The attention of researchers has shifted towards the disruption of cancer cell interactions with the tumor microenvironment. A typical example of such a disruption is the immune checkpoint cancer therapy that disrupts interactions between the immune and the cancer cells. The interaction of cancer antigens with T cells occurs in the immunological synapses. This is characterized by several special features, i.e., the proximity of the immune cells and their target cells, strong intercellular adhesion, and secretion of signaling cytokines into the intercellular cleft. Earlier, we hypothesized that the cancer-associated fibroblasts interacting with cancer cells through a synapse-like adhesion might play an important role in cancer tumors. Studies of the interactions between cancer cells and cancer-associated fibroblasts showed that their clusterization on the membrane surface determined their strength and specificity. The hundreds of interacting pairs are involved in the binding that may indicate the formation of synapse-like structures. These interactions may be responsible for successful metastasis of cancer cells, and their identification and disruption may open new therapeutic possibilities.

Constructing Tumor Immune Microenvironment and Identifying the Immune-Related Prognostic Signatures in Colorectal Cancer Using Multi-omics Data

“…In addition, genes with differentially methylated sites may regulate immune responses through neural signaling pathways such as dendrite development and synapse organization, thereby affecting tumor progression and metastasis. A number of studies also reported similar findings [31][32][33] . Finally, a prognostic prediction model was constructed based on the selected genetic, epigenetic, demographic and clinical variables, which had a superior performance with a higher AUC or C-index value in comparison to the previous prognostic models 14,15 .…”

“…In addition, genes with differentially methylated sites may regulate immune responses through neural signaling pathways such as dendrite development and synapse organization, thereby affecting tumor progression and metastasis. A number of studies also reported similar findings [31][32][33] . Finally, a prognostic prediction model was All rights reserved.…”

From the Catastrophic Objective Irreproducibility of Cancer Research and Unavoidable Failures of Molecular Targeted Therapies to the Sparkling Hope of Supramolecular Targeted Strategies

“…In our previous reviews [51][52][53], we tried to outline the problems of the tumor microenvironment. Here, we briefly repeat some points discussed there, add important new information that has appeared since these publications appeared, and focus mainly on the immune component of tumor stroma.…”

“…The tumor-stroma crosstalk eventually leads to the increased robustness of the tumor. A hypothesis was put forward [51] that such interactions include the formation of synapses and synapse-like structures with the interacting cells positioned at a distance of 10-30 nm [74]. Such a tight intercellular space could enhance the paracrine cross-communication.…”

Expression of EMT-Related Genes in Hybrid E/M Colorectal Cancer Cells Determines Fibroblast Activation and Collagen Remodeling

“…Previously, numerous studies have demonstrated close interactions between different tumor components: cancer cells, the extracellular matrix, and non-cancerous cells associated with tumors, among which CAFs are the most abundant type of cells [35]. Usually, CAFs are described as activated cells with myofibroblast-like morphology distinguishable from that of resident tissue fibroblasts by their elevated production of cytokines, chemokines, metabolites, enzymes, and extracellular matrix components [36].…”