Tunneling Nanotubes Facilitate Intercellular Protein Transfer and Cell Networks Function

Turos-Korgul, Laura; Kolba, Marta D.; Chrościcki, Piotr; Zieminska, A.; Piwocka, Katarzyna

doi:10.3389/fcell.2022.915117

Cited by 15 publications

(6 citation statements)

References 80 publications

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“…The presence of EGFR on the list of ‘borrowed’ genes is intriguing. While we did not investigate transfer of this receptor as RNA or protein, transmembrane and membrane bound proteins have previously been reported to be transferred via TNTs(68). Most of the borrowed genes, however, represent cytoplasmic proteins and/or organelle- or cytoskeleton-associated proteins, which are known to use TNTs as a route for intercellular protein transfer(20, 37, 61).…”

Section: Discussionmentioning

confidence: 99%

Breast Cancers That Disseminate to Bone Marrow Acquire Aggressive Phenotypes through CX43-related Tumor-Stroma Tunnels

Sinha

Callow

Farfel

et al. 2023

Preprint

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Estrogen receptor-positive (ER+) breast cancer commonly disseminates to bone marrow, where interactions with mesenchymal stromal cells (MSCs) shape disease trajectory. We modeled these interactions with tumor-MSC co-cultures and used an integrated transcriptome-proteome-network-analyses workflow to identify a comprehensive catalog of contact-induced changes. Induced genes and proteins in cancer cells, some borrowed and others tumor-intrinsic, were not recapitulated merely by conditioned media from MSCs. Protein-protein interaction networks revealed the rich connectome between ′borrowed′ and ′intrinsic′ components. Bioinformatic approaches prioritized one of the ′borrowed′ components, CCDC88A/GIV, a multi-modular metastasis-related protein which has recently been implicated in driving one of the hallmarks of cancers, i.e., growth signaling autonomy. MSCs transferred GIV protein to ER+ breast cancer cells (that lack GIV) through tunnelling nanotubes via connexin (Cx)43-facilitated intercellular transport. Reinstating GIV alone in GIV-negative breast cancer cells reproduced ~20% of both the ′borrowed′ and the ′intrinsic′ gene induction patterns from contact co-cultures; conferred resistance to anti-estrogen drugs; and enhanced tumor dissemination. Findings provide a multiomic insight into MSC→tumor cell intercellular transport and validate how transport of one such candidate, GIV, from the haves (MSCs) to have-nots (ER+ breast cancer) orchestrates aggressive disease states.

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Section: Discussionmentioning

confidence: 99%

Breast Cancers That Disseminate to Bone Marrow Acquire Aggressive Phenotypes through CX43-related Tumor-Stroma Tunnels

Sinha

Callow

Farfel

et al. 2023

Preprint

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“…The terms related to binding to actin, Ca 2+ , and phospholipids in Figure 3 B, resulted from the identification of proteins associated to the S100 and annexins complexes, probably reflecting the transfer of vesicles [ 40 ]. Other proteins associated with the actin cytoskeleton and regulation of cell shape in Figure 3 A, probably reflect transfer through the actin-rich tunneling nanotubes [ 8 , 9 , 10 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…Mass-spectrometry-based shotgun proteomics allows the identification of individual proteins in complex mixtures by measuring the mass-to-charge ratio ( m / z ) of peptide ions to partially reconstruct their amino acid sequence [ 22 ]. The preferred strategy to study the protein transfer phenomenon is the Trans-SILAC method in which donor cells are cultured in the presence of heavy lysine and arginine isotopologues until a complete label of the proteome, then donor and recipient cells are co-cultured, and finally labeled proteins are detected in enriched recipient cells [ 23 , 24 ]. However, this method requires expensive culture media and is difficult to use in vivo .…”

Section: Introductionmentioning

confidence: 99%

Shotgun Proteomics of Co-Cultured Leukemic and Bone Marrow Stromal Cells from Different Species as a Preliminary Approach to Detect Intercellular Protein Transfer

et al. 2023

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Cellular interactions within the bone marrow microenvironment modulate the properties of subsets of leukemic cells leading to the development of drug-resistant phenotypes. The intercellular transfer of proteins and organelles contributes to this process but the set of transferred proteins and their effects in the receiving cells remain unclear. This study aimed to detect the intercellular protein transfer from mouse bone marrow stromal cells (OP9 cell line) to human T-lymphoblasts (CCRF-CEM cell line) using nanoLC-MS/MS-based shotgun proteomics in a 3D co-culture system. After 24 h of co-culture, 1513 and 67 proteins from human and mouse origin, respectively, were identified in CCRF-CEM cells. The presence of mouse proteins in the human cell line, detected by analyzing the differences in amino acid sequences of orthologous peptides, was interpreted as the result of intercellular transfer. The transferred proteins might have contributed to the observed resistance to vincristine, methotrexate, and hydrogen peroxide in the co-cultured leukemic cells. Our results suggest that shotgun proteomic analyses of co-cultured cells from different species could be a simple option to get a preliminary survey of the proteins exchanged among interacting cells.

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“…This factor can link mitochondrion with the motor complex (Fransson et al, 2006). Phosphorylated Miro1 can stimulate the elimination process of a damaged mitochondrion from the motor protein complex in response to activated mitophagy (Turos‐Korgul et al, 2022). The normal activity of mitochondria is dysregulated under several pathological conditions, leading to oxidative stress and stimulation of excessive autophagy, necrotic changes, and injured cell removal (Galluzzi et al, 2012).…”

Section: Autophagy and Tntsmentioning

confidence: 99%

Angiogenic activity of mitochondria; beyond the sole bioenergetic organelle

Sadeghsoltani,

Hassanpour,

Safari

et al. 2024

Journal Cellular Physiology

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Angiogenesis is a complex process that involves the expansion of the pre‐existing vascular plexus to enhance oxygen and nutrient delivery and is stimulated by various factors, including hypoxia. Since the process of angiogenesis requires a lot of energy, mitochondria play an important role in regulating and promoting this phenomenon. Besides their roles as an oxidative metabolism base, mitochondria are potential bioenergetics organelles to maintain cellular homeostasis via sensing alteration in oxygen levels. Under hypoxic conditions, mitochondria can regulate angiogenesis through different factors. It has been indicated that unidirectional and bidirectional exchange of mitochondria or their related byproducts between the cells is orchestrated via different intercellular mechanisms such as tunneling nanotubes, extracellular vesicles, and gap junctions to maintain the cell homeostasis. Even though, the transfer of mitochondria is one possible mechanism by which cells can promote and regulate the process of angiogenesis under reperfusion/ischemia injury. Despite the existence of a close relationship between mitochondrial donation and angiogenic response in different cell types, the precise molecular mechanisms associated with this phenomenon remain unclear. Here, we aimed to highlight the possible role of mitochondria concerning angiogenesis, especially the role of mitochondrial transport and the possible relation of this transfer with autophagy, the housekeeping phenomenon of cells, and angiogenesis.

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Tunneling Nanotubes Facilitate Intercellular Protein Transfer and Cell Networks Function

Cited by 15 publications

References 80 publications

Breast Cancers That Disseminate to Bone Marrow Acquire Aggressive Phenotypes through CX43-related Tumor-Stroma Tunnels

Breast Cancers That Disseminate to Bone Marrow Acquire Aggressive Phenotypes through CX43-related Tumor-Stroma Tunnels

Shotgun Proteomics of Co-Cultured Leukemic and Bone Marrow Stromal Cells from Different Species as a Preliminary Approach to Detect Intercellular Protein Transfer

Angiogenic activity of mitochondria; beyond the sole bioenergetic organelle

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