Targeting neurons in the tumor microenvironment with bupivacaine nanoparticles reduces breast cancer progression and metastases

Kaduri, Maya; Sela, Mor; Kagan, Shaked; Poley, Maria; Abumanhal-Masarweh, Hanan; Mora-Raimundo, Patricia; Ouro, Alberto; Dahan, Nitsan; Hershkovitz, Dov; Shklover, Jeny; Shainsky‐Roitman, Janna; Buganim, Yosef; Schroeder, Avi

doi:10.1126/sciadv.abj5435

Cited by 26 publications

(20 citation statements)

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“…In conclusion of the role of mGluR8 in cancer, we can highlight that the role played by mGluR8 in neuronal cancer seems to be opposite to the role played in non-neuronal cancer. Neuronal cancer cells release neurotrophic factors and cytokines, that can activate non-neuronal cancer cells leading to their proliferation ( 96 ). Glutamate is a crucial neurotransmitter in the brain; thus, the decreased expression could be harmful, therefore the activation of mGluR8 in the neuronal tumor can be a benefit in decreasing the tumor growth.…”

Section: Role Of Glutamate Receptors In Cancermentioning

confidence: 99%

The role of glutamate receptors in the regulation of the tumor microenvironment

Koda

et al. 2023

Front. Immunol.

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Glutamate, as one of the most important carbon sources in the TCA cycle, is central in metabolic processes that will subsequently influence tumor progression. Several factors can affect the expression of glutamate receptors, playing either a tumor-promoting or tumor-suppressor role in cancer. Thus, the activation of glutamate receptors by the ligand could play a role in tumor development as ample studies have demonstrated the expression of glutamate receptors in a broad range of tumor cells. Glutamate and its receptors are involved in the regulation of different immune cells’ development and function, as suggested by the receptor expression in immune cells. The activation of glutamate receptors can enhance the effectiveness of the effector’s T cells, or decrease the cytokine production in immunosuppressive myeloid-derived suppressor cells, increasing the antitumor immune response. These receptors are essential for the interaction between tumor and immune cells within the tumor microenvironment (TME) and the regulation of antitumor immune responses. Although the role of glutamate in the TCA cycle has been well studied, few studies have deeply investigated the role of glutamate receptors in the regulation of cancer and immune cells within the TME. Here, by a systematic review of the available data, we will critically assess the physiopathological relevance of glutamate receptors in the regulation of cancer and immune cells in the TME and provide some unifying hypotheses for futures research on the role of glutamate receptors in the immune modulation of the tumor.

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Section: Role Of Glutamate Receptors In Cancermentioning

confidence: 99%

The role of glutamate receptors in the regulation of the tumor microenvironment

Koda

et al. 2023

Front. Immunol.

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“…When utilized in conjunction with one another, ECM components such as collagen, fibronectin, and HA can help ease these difficulties ECM. Collagen I, a kind of protein, is frequently employed in the ECM to form hydrogels [170]. Collagen type I hydrogels have aided in our understanding of how the ECM influences cell proliferation and migration, as well as the activity of stromal cells, tumor cells, and their combined activity [60,171].…”

Section: Natural Biomaterialsmentioning

confidence: 99%

Functional biomaterials for biomimetic 3D in vitro tumor microenvironment modeling

Ahmed

2023

In vitro models

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The translational potential of promising anticancer medications and treatments may be enhanced by the creation of 3D in vitro models that can accurately reproduce native tumor microenvironments. Tumor microenvironments for cancer treatment and research can be built in vitro using biomaterials. Three-dimensional in vitro cancer models have provided new insights into the biology of cancer. Cancer researchers are creating artificial three-dimensional tumor models based on functional biomaterials that mimic the microenvironment of the real tumor. Our understanding of tumor stroma activity over the course of cancer has improved because of the use of scaffold and matrix-based three-dimensional systems intended for regenerative medicine. Scientists have created synthetic tumor models thanks to recent developments in materials engineering. These models enable researchers to investigate the biology of cancer and assess the therapeutic effectiveness of available medications. The emergence of biomaterial engineering technologies with the potential to hasten treatment outcomes is highlighted in this review, which also discusses the influence of creating in vitro biomimetic 3D tumor microenvironments utilizing functional biomaterials. Future cancer treatments will rely much more heavily on biomaterials engineering.

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“…As neurons are terminally differentiated, they no longer proliferate, which makes them challenging to maintain in culture. The most common neuronal cell line used in cancer research is PC12, derived from a neuroendocrine tumor in rat adrenal medulla ( Kaduri et al, 2021 ; Kovacs et al, 2020 preprint; Madeo et al, 2018 ; Pundavela et al, 2015 ). PC12 cells can be terminally differentiated into sympathetic-like neurons in the presence of NGF.…”

Section: Current Approaches To Study Nerve–cancer Interactionsmentioning

confidence: 99%

Understanding and modeling nerve–cancer interactions

Oudin

2023

Disease Models &Amp; Mechanisms

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The peripheral nervous system plays an important role in cancer progression. Studies in multiple cancer types have shown that higher intratumoral nerve density is associated with poor outcomes. Peripheral nerves have been shown to directly regulate tumor cell properties, such as growth and metastasis, as well as affect the local environment by modulating angiogenesis and the immune system. In this Review, we discuss the identity of nerves in organs in the periphery where solid tumors grow, the known mechanisms by which nerve density increases in tumors, and the effects these nerves have on cancer progression. We also discuss the strengths and weaknesses of current in vitro and in vivo models used to study nerve–cancer interactions. Increased understanding of the mechanisms by which nerves impact tumor progression and the development of new approaches to study nerve–cancer interactions will facilitate the discovery of novel treatment strategies to treat cancer by targeting nerves.

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Targeting neurons in the tumor microenvironment with bupivacaine nanoparticles reduces breast cancer progression and metastases

Abstract: Targeting neurons in breast cancer with anesthetic nanoparticles inhibits nerve-cancer stimulation and tumor progression.

Cited by 26 publications

References 50 publications

The role of glutamate receptors in the regulation of the tumor microenvironment

The role of glutamate receptors in the regulation of the tumor microenvironment

Functional biomaterials for biomimetic 3D in vitro tumor microenvironment modeling

Understanding and modeling nerve–cancer interactions

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