ECM stiffness-regulated exosomal thrombospondin-1 promotes tunneling nanotubes-based cellular networking in breast cancer cells

Mahadik, Pratiksha; Patwardhan, Sejal

doi:10.1016/j.abb.2023.109624

Cited by 9 publications

(3 citation statements)

References 39 publications

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“…These results confirmed recent data from the literature showing that CD9 and CD81 have minimal impact on the production or composition of EVs in MCF7 cells [82] and that the lack of CD9 does not impair the delivery of the content of EVs into recipient cells [83]. Interestingly, EVs have been shown to regulate TNT formation in mesothelioma, breast cancer or brain endothelial cell models [84][85][86]. Although we cannot completely rule out a crosstalk between EVP and TNT formation or stability, our results together with the current data in literature indicate that CD9 and CD81 deficiencies have a stronger impact on TNT function than on EVP production or function, suggesting that EVPs and TNTs are regulated independently of each other, as far as tetraspanins are concerned.…”

Section: Cd9 and Cd81 Regulate Formation Of Tntssupporting

confidence: 89%

Proteomic landscape of tunneling nanotubes reveals CD9 and CD81 tetraspanins as key regulators

Manzano

Chaze

Rubinstein

et al. 2022

Preprint

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Tunneling nanotubes (TNTs) are open actin- and membrane-based channels, connecting remote cells and allowing direct transfer of cellular material (e.g. vesicles, mRNAs, protein aggregates) from cytoplasm to cytoplasm. Although they are important especially in pathological conditions (e.g., cancers, neurodegenerative diseases), their precise composition and their regulation were still poorly described. Here, using a biochemical approach allowing to separate TNTs from cell bodies and from extracellular vesicles and particles (EVPs), we obtained the full composition of TNTs compared to EVPs. We then focused to two major components of our proteomic data, the CD9 and CD81 tetraspanins, and further investigated their specific roles in TNT formation and function. We show that these two tetraspanins have distinct functions: CD9 participates in the initiation of TNTs, whereas CD81 expression is required to allow the functional transfer of vesicle in the newly formed TNTs, possibly by regulating fusion with the opposing cell.

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Section: Cd9 and Cd81 Regulate Formation Of Tntssupporting

confidence: 89%

Proteomic landscape of tunneling nanotubes reveals CD9 and CD81 tetraspanins as key regulators

Manzano

Chaze

Rubinstein

et al. 2022

Preprint

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“…Furthermore, CAFs are valuable in the clinical diagnosis of breast cancer, as well as in therapy and prediction of prognosis. However, many aspects remain unclear, including the relationship between CAFs and other mesenchymal cells or stroma structures, such as tunneling nanotubes, which are made by exosomes derived from breast cancer cells but not CAFs ( 185 ), the precise mechanism of their escape from immune attack, and whether other valuable molecular markers of CAFs exist. The breast cancer immune-microenvironment with tumor-associated tertiary lymphoid structure (TA-TLS) usually have a higher representation of tumor-infiltrating lymphocytes (TIL) and show a better response to chemotherapy and immunotherapy ( 186 ).…”

Section: Conclusion and Prospecsmentioning

confidence: 99%

The role of cancer-associated fibroblasts in breast cancer metastasis

Wang

Huang

et al. 2023

Front. Oncol.

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Breast cancer deaths are primarily caused by metastasis. There are several treatment options that can be used to treat breast cancer. There are, however, a limited number of treatments that can either prevent or inhibit the spread of breast tumor metastases. Thus, novel therapeutic strategies are needed. Studies have increasingly focused on the importance of the tumor microenvironment (TME) in metastasis of breast cancer. As the most abundant cells in the TME, cancer-associated fibroblasts (CAFs) play important roles in cancer pathogenesis. They can remodel the structure of the extracellular matrix (ECM) and engage in crosstalk with cancer cells or other stroma cells by secreting growth factors, cytokines, and chemokines, as well as components of the ECM, which assist the tumor cells to invade through the TME and cause distant metastasis. Clinically, CAFs not only foster the initiation, growth, angiogenesis, invasion, and metastasis of breast cancer but also serve as biomarkers for diagnosis, therapy, and prediction of prognosis. In this review, we summarize the biological characteristics and subtypes of CAFs and their functions in breast cancer metastasis, focusing on their important roles in the diagnosis, prognosis, and treatment of breast cancer. Recent studies suggest that CAFs are vital partners of breast cancer cells that assist metastasis and may represent ideal targets for prevention and treatment of breast cancer metastasis.

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“…The study of Mentor and Fisher suggested TNT-mediated trans-permeability between BEC cells. Recently another study has shown that thrombospondin-1-containing exosomes released from breast cancer cells promote biogenesis of TNTs (Mahadik and Patwardhan, 2023 ). Furthermore, exosomes utilize TNTs as vehicles for efficient long-distance transfer of selective cargo to the recipient cells (Thayanithy et al, 2014 ).…”

mentioning

confidence: 99%

Editorial: Synergistic interactions between exosomes and tunneling nanotubes in long-range intercellular transfer

Nath,

Pountney,

Neuzil

2023

Front. Mol. Neurosci.

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ECM stiffness-regulated exosomal thrombospondin-1 promotes tunneling nanotubes-based cellular networking in breast cancer cells

Cited by 9 publications

References 39 publications

Proteomic landscape of tunneling nanotubes reveals CD9 and CD81 tetraspanins as key regulators

Proteomic landscape of tunneling nanotubes reveals CD9 and CD81 tetraspanins as key regulators

The role of cancer-associated fibroblasts in breast cancer metastasis

Editorial: Synergistic interactions between exosomes and tunneling nanotubes in long-range intercellular transfer

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