The Role of Cell Adhesion, Cell Junctions, and Extracellular Matrix in Development and Carcinogenesis

Santos, Anderson K.; Tonelli, Fernanda Maria Policarpo; Silva, Daniel A. F.; Gomes, Kátia N.; Ladeira, Luiz Orlando; Resende, Rodrigo R.

doi:10.1007/978-94-007-6211-4_2

Cited by 8 publications

(3 citation statements)

References 92 publications

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“…Intercellular recognition between two opposing membranes, therefore, requires large multivalent arrays (clusters) consisting of hundreds, or even thousands, of receptors that increase the total avidity of the interaction with the ligands to a point high enough to prompt a signaling event [88,91]. For example, T cells are capable of detecting a single ligand on antigen-presenting cells; however, nearly ten of them are necessary for T cell activation [92]. As for signaling by secreted ligands, the range of signaling elicited by the ligand-producing cell can span tens of cell diameters.…”

Section: Two Postulate Principlementioning

confidence: 99%

The Untouched Reserve of Cancer Chemotherapy: Tumor Cell Communication as a Promising Supramolecular Target

Alekseenko,

Zhukova,

Kondratyeva

et al. 2024

Preprint

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52 years have passed since President Nixon launched the "War on Cancer". The goals outlined by the President were not achieved because cancer treatment applied such as chemotherapy, radiotherapy, and targeted therapy have not fully met expectations. We suggest a new chemotherapeutic strategy: disrupting the communication between cancer cells and their microenvironment by chemical means. Immunological synapses that form between cancer cells and immune or other stromal cells provide an attractive target for this approach. Synapses form ligand-receptor clusters within interface of the interacting cells. Despite their differences, synapses share common properties: intercellular protein clusters; the proximity of these proteins; and their cooperative interaction making a synapse an unified functional unit. Synapses provide the limited space for the focused intercellular exchange of signaling molecules and particles. Therefore, destruction of synapses is expected to cause collapse of various tumor types. Additionally, the clustered arrangement of synapse components offers opportunities to increase treatment safety by reducing the concentration of cell impermeable agents used, to enhance its specificity applying cross-linking reagents, thus restricting modifications of surface-exposed molecules. By attaching a cleavable cell permeable toxic agent to a crosslinker should further enhance a killing potential in treating cancer. The proposed approach promises to be simple, universal, and less expensive than existing cancer therapy methods.

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Section: Two Postulate Principlementioning

confidence: 99%

The Untouched Reserve of Cancer Chemotherapy: Tumor Cell Communication as a Promising Supramolecular Target

Alekseenko,

Zhukova,

Kondratyeva

et al. 2024

Preprint

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“…Cell adhesion and junction proteins. These molecules are often in a gray area of categorization because they participate not just in cell adhesion and locomotion, but also in a broad range of cancer-relevant processes including cell-cell and intracellular signaling, cell growth/proliferation/differentiation and death, secretion, angiogenesis, endocytosis, and chemotaxis, just to name a few (Figures 6B and 6Cc) (50). The CAM receptors that are involved in signaling belong to several families that include Ca-dependent cadherins, integrins, selectins, and Ca-independent immunoglobulin-like proteins.…”

Section: Immune System Receptors Cds and Antigen Characteristicsmentioning

confidence: 99%

The SKBR3 Cell-Membrane Proteome: Role in Aberrant Cancer Cell Proliferation and Resource for Precision Medicine Applications

Karcini¹,

Lazar

2021

Preprint

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The plasma membrane proteome resides at the interface between the extra- and intra-cellular environment and through its various roles in signal transduction, immune recognition, nutrient transport, and cell-cell and cell-matrix interactions plays an absolutely critical role in determining the fate of a cell. Our work was aimed at exploring the landscape of the cancer cell-membrane proteome responsible for sustaining uncontrolled cell proliferation, and its intrinsic resources for enabling detection and therapeutic interventions. SKBR3/HER2+ breast cancer cells were used as a model system and mass spectrometry for characterizing the proteome. The number of identified cell-membrane proteins exceeded 2,000, with ~1,300 being matched by two or more unique peptides. Classification in four major categories, i.e., proteins with receptor or enzymatic activity, CD antigens, transporters, and cell adhesion proteins, uncovered overlapping roles in biological processes that drive cell growth, apoptosis, differentiation, immune response, adhesion and migration, as well as capabilities for signaling crosstalk and alternate pathways for proliferation. The large number of tumor markers (>50) and putative drug targets (>100) exposed a vast potential for yet unexplored detection and targeting opportunities, whereas the presence of 15 antigen immunological markers enabled an assessment of epithelial, mesenchymal or stemness characteristics. Serum-starved cells displayed altered processes related to mitochondrial OXPHOS/ATP synthesis, protein folding and localization, while serum-treated cells exhibited attributes that support tissue invasion and metastasis. Altogether, our findings advance the understanding of the biological triggers that sustain aberrant cancer cell proliferation, survival and development of resistance to therapeutic drugs, and reveal the vast innate opportunities for guiding immunological profiling and precision medicine applications aimed at target selection or drug discovery.

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“…Anoikis is a form of programmed cell death that occurs due to the loss of anchorage-dependent attachment to the extracellular matrix (ECM) [ 26 , 27 ]. Because cell-cell adhesion through the ECM plays an important role in cell activities, proliferation, and survival [ 28 ], a low propensity to adhere to the host cells due to a loss of matrix anchorage may induce the death of the transplanted MSCs. Although several ongoing studies are focused on improving MSC survival, no potential solutions have been suggested to solve the underlying problem of weak adhesion.…”

Section: Introductionmentioning

confidence: 99%

Cell Adhesion and Long-Term Survival of Transplanted Mesenchymal Stem Cells: A Prerequisite for Cell Therapy

Lee

Choi

Cha

et al. 2015

Oxidative Medicine and Cellular Longevity

198

153

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The literature provides abundant evidence that mesenchymal stem cells (MSCs) are an attractive resource for therapeutics and have beneficial effects in regenerating injured tissues due to their self-renewal ability and broad differentiation potential. Although the therapeutic potential of MSCs has been proven in both preclinical and clinical studies, several questions have not yet been addressed. A major limitation to the use of MSCs in clinical applications is their poor viability at the site of injury due to the harsh microenvironment and to anoikis driven by the loss of cell adhesion. To improve the survival of the transplanted MSCs, strategies to regulate apoptotic signaling and enhance cell adhesion have been developed, such as pretreatment with cytokines, growth factors, and antiapoptotic molecules, genetic modifications, and hypoxic preconditioning. More appropriate animal models and a greater understanding of the therapeutic mechanisms of MSCs will be required for their successful clinical application. Nevertheless, the development of stem cell therapies using MSCs has the potential to treat degenerative diseases. This review discusses various approaches to improving MSC survival by inhibiting anoikis.

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The Role of Cell Adhesion, Cell Junctions, and Extracellular Matrix in Development and Carcinogenesis

Cited by 8 publications

References 92 publications

The Untouched Reserve of Cancer Chemotherapy: Tumor Cell Communication as a Promising Supramolecular Target

The Untouched Reserve of Cancer Chemotherapy: Tumor Cell Communication as a Promising Supramolecular Target

The SKBR3 Cell-Membrane Proteome: Role in Aberrant Cancer Cell Proliferation and Resource for Precision Medicine Applications

Cell Adhesion and Long-Term Survival of Transplanted Mesenchymal Stem Cells: A Prerequisite for Cell Therapy

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