Tumor-associated macrophages and Schwann cells promote perineural invasion via paracrine loop in pancreatic ductal adenocarcinoma

Zhang, Bin; Guo, Xiaofeng; Ye, Huilin; Huang, Liqin; Zhang, Yuting; Li, Zhiguo; Su, Dan; Lin, Ling; Zhou, Peng; Lu, Yanan; Chen, Rufu; Zhou, Quanbo

doi:10.21203/rs.3.rs-2060535/v1

Cited by 2 publications

(1 citation statement)

References 29 publications

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“…Nerves can not only serve as a route of cancer spread [ 310 ], but also remodel lymph vasculature to promote tumour cell dissemination [ 311 ]. Moreover, neurons and glial cells communicate directly with malignant cells or other cellular components in the TME through paracrine factors and, in some cases, through neuron-to-cancer cell synapses, to promote metastasis [ 312 , 313 ]. To delineate the mechanisms of cancer dissemination along nerves, it has been proposed that the nerve-cancer cell crosstalk in perineural niche should be considered part of the TME while exploring [ 314 , 315 ].…”

Section: Tumor Biology Of Exosomesmentioning

confidence: 99%

Role of Exosomes in Cancer and Aptamer-Modified Exosomes as a Promising Platform for Cancer Targeted Therapy

Wu,

Cao,

Chen

et al. 2024

Biol Proced Online

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Exosomes are increasingly recognized as important mediators of intercellular communication in cancer biology. Exosomes can be derived from cancer cells as well as cellular components in tumor microenvironment. After secretion, the exosomes carrying a wide range of bioactive cargos can be ingested by local or distant recipient cells. The released cargos act through a variety of mechanisms to elicit multiple biological effects and impact most if not all hallmarks of cancer. Moreover, owing to their excellent biocompatibility and capability of being easily engineered or modified, exosomes are currently exploited as a promising platform for cancer targeted therapy. In this review, we first summarize the current knowledge of roles of exosomes in risk and etiology, initiation and progression of cancer, as well as their underlying molecular mechanisms. The aptamer-modified exosome as a promising platform for cancer targeted therapy is then briefly introduced. We also discuss the future directions for emerging roles of exosome in tumor biology and perspective of aptamer-modified exosomes in cancer therapy.

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Section: Tumor Biology Of Exosomesmentioning

confidence: 99%

Role of Exosomes in Cancer and Aptamer-Modified Exosomes as a Promising Platform for Cancer Targeted Therapy

Wu,

Cao,

Chen

et al. 2024

Biol Proced Online

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Glial cell-derived soluble factors increase the metastatic potential of pancreatic adenocarcinoma cells and induce epithelial-to-mesenchymal transition

García-Reyes

Kuzmanov

Schneider

et al. 2023

J Cancer Res Clin Oncol

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Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive types of cancer, characterized by the spreading of highly metastatic cancer cells, including invasion into surrounding nerves and perineural spaces. Nerves, in turn, can invade the tumor tissue and, through the secretion of neurotrophic factors, chemokines, and cytokines, contribute to PDAC progression. However, the contribution of the nerve-associated glial cells to PDAC progression is not well characterized. Methods Two murine PDAC cell lines were cultured with the conditioned media (CM) of primary enteric glial cells or IMS32 Schwann cells (SCs). Different properties of PDAC cells, such as invasiveness, migratory capacity, and resistance to gemcitabine, were measured by RT-qPCR, microscopy, and MTT assays. Using a neuronal cell line, the observed effects were confirmed to be specific to the glial lineage. Results Compared to the control medium, PDAC cells in the glial cell-conditioned medium showed increased invasiveness and migratory capacity. These cells showed reduced E-cadherin and increased N-cadherin and Vimentin levels, all markers of epithelial–mesenchymal transition (EMT). Primary enteric glial cell CM inhibited the proliferation of PDAC cells but preserved their viability, upregulated transcription factor Snail, and increased their resistance to gemcitabine. The conditioned medium generated from the IMS32 SCs produced comparable results. Conclusion Our data suggest that glial cells can increase the metastatic potential of PDAC cells by increasing their migratory capacity and inducing epithelial-to-mesenchymal transition, a re-programming that many solid tumors use to undergo metastasis. Glial cell-conditioned medium also increased the chemoresistance of PDAC cells. These findings may have implications for future therapeutic strategies, such as targeting glial cell-derived factor signaling in PDAC.

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Tumor-associated macrophages and Schwann cells promote perineural invasion via paracrine loop in pancreatic ductal adenocarcinoma

Cited by 2 publications

References 29 publications

Role of Exosomes in Cancer and Aptamer-Modified Exosomes as a Promising Platform for Cancer Targeted Therapy

Role of Exosomes in Cancer and Aptamer-Modified Exosomes as a Promising Platform for Cancer Targeted Therapy

Glial cell-derived soluble factors increase the metastatic potential of pancreatic adenocarcinoma cells and induce epithelial-to-mesenchymal transition

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