Tunneling Nanotubes: Intercellular Conduits for Direct Cell-to-Cell Communication in Cancer

Lou, Emil; Subramanian, Subbaya

doi:10.1007/978-94-017-7380-5_8

Cited by 3 publications

(2 citation statements)

References 122 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is probable that future studies will more clearly elucidate the role of TNTs as critical effectors in the pathophysiology of disease(s). Thus, it is reasonable to postulate that disrupting or preventing TNT‐mediated communication by targeted drugs or other means will present a novel therapeutic strategy . However, it would also be critical to identify mechanisms and genetics that underlie TNT biogenesis.…”

Section: Elucidating Modes Of Intercellular Communication: Tunneling mentioning

confidence: 99%

Lost in translation: applying 2D intercellular communication via tunneling nanotubes in cell culture to physiologically relevant 3D microenvironments

et al. 2016

Self Cite

View full text Add to dashboard Cite

Tunneling nanotubes (TNTs) are membranous conduits for direct cell-to-cell communication. Until the past decade, little had been known about their composite structure, function, and mechanisms of action in both normal physiologic conditions as well as in disease states. Now TNTs are attracting increasing interest for their key role(s) in the pathogenesis of disease, including neurodegenerative disorders, inflammatory and infectious diseases, and cancer. The field of TNT biology is still in its infancy, but inroads have been made in determining potential mechanisms and function of these remarkable structures. For example, TNTs function as critical conduits for cellular exchange of information; thus, in cancer, they may play an important role in critical pathophysiologic features of the disease, including cellular invasion, metastasis, and emergence of chemotherapy drug resistance. Although the TNT field is still in a nascent stage, we propose that TNTs can be investigated as novel targets for drug-based treatment of cancer and other diseases.

show abstract

Section: Elucidating Modes Of Intercellular Communication: Tunneling mentioning

confidence: 99%

Lost in translation: applying 2D intercellular communication via tunneling nanotubes in cell culture to physiologically relevant 3D microenvironments

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…This lack of a distinct biomarker has presented a challenge to this emerging field of cell biology. Thus, identification of TNTs has relied on visual identification of structural characteristics, including connections between two or more cells and the non-adherent nature of their protrusion 'bridges' when cells are cultured in vitro [29,54,59,60,[62][63][64][65][66][67]; this latter feature helps to distinguish TNTs from other actin-based protrusions that adhere to the substratum in in vitro tissue culture and are more often associated with cell motility rather than cell-cell communication [67][68][69]. Manual visual identification of TNTs is a tedious and arduous process that also introduces the potential for lack of reproducibility.…”

Section: Introductionmentioning

confidence: 99%

TNTdetect.AI: A Deep Learning Model for Automated Detection and Counting of Tunneling Nanotubes in Microscopy Images

Ceran

Ergüder

Ladner

et al. 2022

Cancers

Self Cite

View full text Add to dashboard Cite

Background: Tunneling nanotubes (TNTs) are cellular structures connecting cell membranes and mediating intercellular communication. TNTs are manually identified and counted by a trained investigator; however, this process is time-intensive. We therefore sought to develop an automated approach for quantitative analysis of TNTs. Methods: We used a convolutional neural network (U-Net) deep learning model to segment phase contrast microscopy images of both cancer and non-cancer cells. Our method was composed of preprocessing and model development. We developed a new preprocessing method to label TNTs on a pixel-wise basis. Two sequential models were employed to detect TNTs. First, we identified the regions of images with TNTs by implementing a classification algorithm. Second, we fed parts of the image classified as TNT-containing into a modified U-Net model to estimate TNTs on a pixel-wise basis. Results: The algorithm detected 49.9% of human expert-identified TNTs, counted TNTs, and calculated the number of TNTs per cell, or TNT-to-cell ratio (TCR); it detected TNTs that were not originally detected by the experts. The model had 0.41 precision, 0.26 recall, and 0.32 f-1 score on a test dataset. The predicted and true TCRs were not significantly different across the training and test datasets (p = 0.78). Conclusions: Our automated approach labeled and detected TNTs and cells imaged in culture, resulting in comparable TCRs to those determined by human experts. Future studies will aim to improve on the accuracy, precision, and recall of the algorithm.

show abstract

Chemotherapy-Induced Tunneling Nanotubes Mediate Intercellular Drug Efflux in Pancreatic Cancer

Desir

O’Hare

Vogel

et al. 2018

Sci Rep

Self Cite

View full text Add to dashboard Cite

Intercellular communication plays a critical role in the ever-evolving landscape of invasive cancers. Recent studies have elucidated the potential role of tunneling nanotubes (TNTs) in this function. TNTs are long, filamentous, actin-based cell protrusions that mediate direct cell-to-cell communication between malignant cells. In this study, we investigated the formation of TNTs in response to variable concentrations of the chemotherapeutic drug doxorubicin, which is used extensively in the treatment of cancer patients. Doxorubicin stimulated an increased formation of TNTs in pancreatic cancer cells, and this occurred in a dose-dependent fashion. Furthermore, TNTs facilitated the intercellular redistribution of this drug between connected cells in both pancreatic and ovarian cancer systems in vitro. To provide supportive evidence for the relevance of TNTs in pancreatic cancer in vivo, we performed multiphoton fluorescence microscopy and imaged TNTs in tumor specimens resected from three human patients with pancreatic adenocarcinoma, and one with neuroendocrine carcinoma. In sum, TNT formation was upregulated in aggressive forms of pancreatic carcinoma, was further stimulated after chemotherapy exposure, and acted as a novel method for drug efflux. These findings implicate TNTs as a potential novel mechanism of drug resistance in chemorefractory forms of cancer.

show abstract

Tunneling Nanotubes: Intercellular Conduits for Direct Cell-to-Cell Communication in Cancer

Cited by 3 publications

References 122 publications

Lost in translation: applying 2D intercellular communication via tunneling nanotubes in cell culture to physiologically relevant 3D microenvironments

Lost in translation: applying 2D intercellular communication via tunneling nanotubes in cell culture to physiologically relevant 3D microenvironments

TNTdetect.AI: A Deep Learning Model for Automated Detection and Counting of Tunneling Nanotubes in Microscopy Images

Chemotherapy-Induced Tunneling Nanotubes Mediate Intercellular Drug Efflux in Pancreatic Cancer

Contact Info

Product

Resources

About