bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2025–05–18
seven papers selected by
Maksym V. Kopanitsa, Charles River Laboratories
  1. Interplay Between Schwann Cells and Peripheral Cancers: Mechanisms and Therapeutic Targets in Cancer Progression.
  2. Genomic profiling and pathological assessment of malignant peripheral nerve sheath tumors.
  3. Activated Schwann cells promote tumor growth in colon cancer.
  4. Nervous system in hepatocellular carcinoma: Correlation, mechanisms, therapeutic implications, and future perspectives.
  5. Nervous system-gut microbiota-immune system axis: future directions for preventing tumor.
  6. Brain structural alterations and cognitive dysfunction in lung cancer patients without brain metastasis.
  7. LINC01614 enhances neural invasion and gastric cancer progression by stabilizing VCAM1 and activating the AKT/mTOR pathway.
  1. Glia. 2025 May 10.
    Interplay Between Schwann Cells and Peripheral Cancers: Mechanisms and Therapeutic Targets in Cancer Progression.
    Ziwan He, Furui Liu, Lin Lin, Zhihui Huang, Yongjie Wang.
      Cancer, a leading global health concern, is characterized by uncontrolled proliferation of cells, high invasion into surrounding tissues, and eventual metastasis to distant organs. The complexity of cancer is further amplified by diverse cellular components within the tumor microenvironment (TME), encompassing both cancerous and non-cancerous cells that fuel tumorigenesis and progression. Schwann cells (SCs), the main glial cells of the peripheral nervous system, have emerged as crucial components within the TME in cancer development. Here, we summarize the multifaceted roles of SCs in tumor growth, epithelial-mesenchymal transition, perineural invasion, and chemotherapy resistance. This review focuses on the effects of SCs on eight distinct peripheral cancer types, particularly pancreatic, lung, and colorectal cancers, along with cancer-related pain, one of the most common symptoms that affect quality of life and prognosis in cancer patients. Furthermore, we emphasize the therapeutic potential of SCs by delving into advanced technologies and clinical strategies related to SCs, which make us advocate for further research to elucidate the events and molecular mechanisms underlying the SC-cancer relationship. Translating these insights into clinical applications may offer new hope for improved cancer management and patient outcomes.
    Keywords:  Schwann cell; cancer; cancer pain; crosstalk; therapeutic targets
    DOI:  https://doi.org/10.1002/glia.70032
  2. J Cancer Res Clin Oncol. 2025 May 14. 151(5): 165
    Genomic profiling and pathological assessment of malignant peripheral nerve sheath tumors.
    Qian Cui, Fen Zhang, Jian Liu, Jie Xu, Hongmei Wu, Fangping Xu, Qingling Zhang.
       PURPOSE: Addressing the significant clinical challenges associated with managing malignant peripheral nerve sheath tumor (MPNST), this study focuses on the difficulties encountered in achieving accurate pathological diagnosis and the exploration of effective treatment options through genomic analysis.
    METHODS: The study included 20 patients with an initial pathological diagnosis of MPNST. Next-generation sequencing-based genomic analysis was conducted to assess the molecular features of MPNST, specifically looking for somatic mutations and actionable mutations.
    RESULTS: The genomic analysis resulted in diagnostic refinement or reassignment for 20% of the cases. Somatic mutations were predominantly enriched in the RTK/RAS pathway, accounting for 64.7% of the findings. Additionally, actionable mutations were identified in 70.6% of patients who had a confirmed diagnosis of MPNST. Notably, the study revealed the presence of altered genes that were absent in Western populations, suggesting potential ethnic differences and the opportunity for alternative treatment strategies. Furthermore, patients with CDKN2A mutations exhibited significantly shorter disease-free survival compared to those without such mutations, with median survival times of 6.08 months versus 14.3 months (p = 0.0038).
    CONCLUSION: The findings emphasize the necessity of molecular testing for accurate diagnosis of MPNST, which can guide optimal therapeutic options and highlight the need for tailored treatment strategies considering the heterogeneity of pathological phenotypes and molecular features among patients.
    Keywords:  Actionable genes; Differential diagnosis; MPNST; Molecular feature
    DOI:  https://doi.org/10.1007/s00432-025-06209-7
  3. Cancer Lett. 2025 May 10. pii: S0304-3835(25)00358-1. [Epub ahead of print]626 217791
    Activated Schwann cells promote tumor growth in colon cancer.
    Kexin He, Hao Wang, Hao Wu, Weihan Li, Ruixue Huo, Luju Jiang, Minhao Yu, Junli Xue.
      Schwann cells, traditionally recognized as glial cells of the peripheral nervous system, have emerged as pivotal cellular constituents within the tumor microenvironment. Colon cancer exhibits significant nerve dependence; however, the roles of Schwann cells in colon cancer progression remain insufficiently understood. Here, we identified a significant increase in tumor-associated nonmyelinating Schwann cells within colon tumor samples compared to their normal tissue counterparts. Furthermore, the elevated abundance of these cells was associated with poorer clinical outcomes in colon cancer. Within colon tumor tissues, Schwann cells displayed elevated expression of c-Jun, a key gene involved in their activation and reprogramming. Knocking down c-Jun hampered Schwann cell activation. Single-cell RNA sequencing analysis uncovered that glial cells engage in the most robust cell-cell interactions with malignant cells and fibroblasts. Co-culture experiments demonstrated that tumor cells and cancer-associated fibroblasts specifically promoted c-Jun activation in Schwann cells, whereas co-culture with immune cells did not elicit a similar response. Under In vivo conditions, Schwann cells enhance tumor growth in a c-Jun-dependent manner. Moreover, c-Jun knockout in Schwann cells orchestrated a reprogramming of their secretome, exemplified by a notable reduction in IL-6, a key effector of their tumor-promoting activity. Collectively, our study elucidates the critical role of activated Schwann cells in colon cancer, which may offer a novel therapeutic strategy for treatment.
    Keywords:  Cancer neuroscience; Colon adenocarcinoma; Colorectal cancer; Tumor-associated schwann cells
    DOI:  https://doi.org/10.1016/j.canlet.2025.217791
  4. Biochim Biophys Acta Rev Cancer. 2025 May 10. pii: S0304-419X(25)00087-3. [Epub ahead of print] 189345
    Nervous system in hepatocellular carcinoma: Correlation, mechanisms, therapeutic implications, and future perspectives.
    Wenxuan Li, Jinghao Zhang, Yueqiu Gao, Xiaoni Kong, Xuehua Sun.
      Hepatocellular carcinoma (HCC) is a highly heterogeneous and complex cancer influenced by both the tumor microenvironment and multi-level regulation of the nervous system. Increasing evidence highlights critical roles of the central nervous system (CNS) and peripheral nervous system (PNS) in modulating HCC progression. Psychological stress and emotional disturbances, representing CNS dysregulation, directly accelerate tumor growth, metastasis, and impair anti-tumor immunity in HCC. PNS involvement, particularly autonomic innervation, extensively reshapes the hepatic tumor microenvironment; specifically, sympathetic activation promotes immune suppression, tumor cell proliferation, epithelial-mesenchymal transition (EMT), and cancer stemness via β-adrenergic signaling and hypoxia-inducible factor 1-alpha (HIF-1α) stabilization, whereas parasympathetic signals generally exert anti-inflammatory and tumor-suppressive effects mediated by acetylcholine. Neurotransmitters including epinephrine, norepinephrine, dopamine, serotonin, and acetylcholine precisely regulate critical pathways such as AKT/mTOR, ERK, and NF-κB, thereby driving malignant cell behaviors, immune evasion, and chemoresistance. Neuro-targeted pharmacological interventions (e.g., SSRIs, β-blockers, dopamine antagonists) and behavioral therapies have shown efficacy in preclinical studies, underscoring their therapeutic potential. Additionally, neural-associated biomarkers like NEDD9, CNTN1, and nerve growth factor (NGF) exhibit prognostic significance, supporting their future clinical application. By systematically integrating neuroscience with oncology, this review identifies innovative neural-based therapeutic strategies, highlights key mechanistic insights, and outlines promising directions for future research and personalized clinical management of HCC.
    Keywords:  Hepatocellular carcinoma; Nervous system; Neurotransmitters; Therapeutic implications; Tumor microenvironment
    DOI:  https://doi.org/10.1016/j.bbcan.2025.189345
  5. Front Immunol. 2025 ;16 1535955
    Nervous system-gut microbiota-immune system axis: future directions for preventing tumor.
    Juanjuan Wang, Wenyue Cheng, Rongcun Yang.
      Tumor is one of the leading causes of death worldwide. The occurrence and development of tumors are related to multiple systems and factors such as the immune system, gut microbiota, and nervous system. The immune system plays a critical role in tumor development. Studies have also found that the gut microbiota can directly or indirectly affect tumorigenesis and tumor development. With increasing attention on the tumor microenvironment in recent years, the nervous system has emerged as a novel regulator of tumor development. Some tumor therapies based on the nervous system have also been tested in clinical trials. However, the nervous system can not only directly interact with tumor cells but also indirectly affect tumor development through the gut microbiota. The nervous system-mediated gut microbiota can regulate tumorigenesis, growth, invasion, and metastasis through the immune system. Here, we mainly explore the potential effects of the nervous system-gut microbiota-immune system axis on tumorigenesis and tumor development. The effects of the nervous system-gut microbiota-immune system axis on tumors involve the nervous system regulating immune cells through the gut microbiota, which can prevent tumor development. Meanwhile, the direct effects of the gut microbiota on tumors and the regulation of the immune system by the nervous system, which can affect tumor development, are also reviewed.
    Keywords:  gut microbiota; immune cells; nervous system; signal transduction; tumor environment
    DOI:  https://doi.org/10.3389/fimmu.2025.1535955
  6. Sci Rep. 2025 May 11. 15(1): 16366
    Brain structural alterations and cognitive dysfunction in lung cancer patients without brain metastasis.
    Da-Fu Zhang, Huan Ma, Zhi-Ping Zhang, Jing Ai, Zong-Sheng Pu, Yi-Fan Liu, Wen-Ting Cao, Zhen-Hui Li.
      This study explored the relationship between cognitive function and brain structure in lung cancer (LCs) patients without brain metastases and healthy controls (HCs). A cohort of 75 chemotherapy-naive LCs without brain metastases and 29 age-, sex-, and education-matched HCs underwent cognitive assessments and structural MRI. The MRI focused on cortical thickness, surface area, and volume of subcortical structures. We examined the relationships among these parameters. The volume of twelve subcortical structures was significantly reduced in patients with advanced-stage lung cancer (aLCs) compared to HCs (p < 0.05). In aLCs, cortical thickness decreased in one brain region and surface area in five regions (p < 0.05). Patients with early-stage lung cancer (eLCs) exhibited increased cortical thickness in three regions. When comparing eLCs to aLCs, there was a notable decrease in cortical thickness and surface area (p < 0.05). Visuospatial/executive and delayed memory functions were impaired in aLCs and worsened with disease progression. These impairments correlated positively with the thickness of several cerebral cortices and the surface area and volume of subcortical structures (p < 0.05). Structural brain changes and cognitive dysfunction are evident in aLC patients, independent of metastasis. Since none of the patients received chemotherapy, the observed abnormalities in aLCs, absent in eLCs, are likely attributable to the disease itself rather than chemotherapy effects.
    DOI:  https://doi.org/10.1038/s41598-025-99326-9
  7. Cell Signal. 2025 May 09. pii: S0898-6568(25)00275-X. [Epub ahead of print] 111860
    LINC01614 enhances neural invasion and gastric cancer progression by stabilizing VCAM1 and activating the AKT/mTOR pathway.
    Yujing Liu, Qian Li, Yongyou Wu, Hongjie Tang, Chen Zou, Wenhuan Dou, Guoqiang Zhang.
       BACKGROUND: Gastric cancer (GC) is among the most fatal cancers worldwide. Neural infiltration (NI) is a poorly understood metastatic pathway with limited insights into its regulation and therapeutic targets.
    METHODS: The GEPIA algorithm and RBPsuite analyzed the LINC01614-IGF2BP3-VCAM1 axis in the TCGA-STAD dataset. GC-NI clinical samples and cell lines validated LINC01614 expression and its clinical relevance. CCK-8, colony formation, flow cytometry, Transwell migration and dorsal root ganglia (DRG)-GC co-culture assays assessed LINC01614's role in cell proliferation, apoptosis, migration, invasion and NI. RNA immunoprecipitation, RNA pull-down combined with mass spectrometry, actinomycin D stability assays, and fluorescence in situ hybridization elucidated the formation of an RNA-protein ternary complex and its regulatory effects on VCAM1 stability and the AKT/mTOR pathway. An in vivo murine model was established to examine the impact of LINC01614 knockdown on tumor growth and NI, with tumor progression tracked using IVIS spectral imaging and immunohistochemical staining of GP9.5.
    RESULTS: LINC01614 was significantly overexpressed in GC-NI-positive patients and correlated with poor prognosis, as validated in clinical samples and TCGA-STAD datasets. Functional assays demonstrated that LINC01614 knockdown inhibited GC cell proliferation, migration, invasion, and NI potential. Mechanistically, RNA pull-down followed by mass spectrometry identified IGF2BP3 as a key binding partner of LINC01614. Subsequent RNA immunoprecipitation assays showed that LINC01614 interacts with IGF2BP3 to form an RNA-protein ternary complex with VCAM1 in the nucleus, as further validated by fluorescence in situ hybridization-immunofluorescence. This complex stabilized VCAM1 mRNA, as demonstrated by actinomycin D assays, leading to its upregulation. Enhanced VCAM1 expression activated the AKT/mTOR pathway, which drove tumor progression and NI. Knockdown of LINC01614 disrupted this axis, reduced VCAM1 levels, attenuated AKT/mTOR pathway activation, and mitigated the malignant phenotype of GC cells.
    CONCLUSION: LINC01614 drives NI in GC by stabilizing VCAM1 and activating the AKT/mTOR pathway, making it a promising biomarker and therapeutic target.
    Keywords:  AKT/mTOR; Gastric cancer; Invasion; LINC01614-IGF2BP3-VCAM1 RNA-protein ternary complex; Neural invasion
    DOI:  https://doi.org/10.1016/j.cellsig.2025.111860
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