bims-metorg 2026-01-04 papers

bims-metorg

Biomed News

on Metabolism and Organotropism

Issue of 2026–01–04
seven papers selected by
Bruna Martins Garcia, CABIMER

The Role of Extracellular Proteases and Extracellular Matrix Remodeling in the Pre-Metastatic Niche.
Microenvironmental and Molecular Pathways Driving Dormancy Escape in Bone Metastases.
A novel tool to predict the probability of pulmonary metastasis in patients with primary osseous sacral/pelvic tumors: a large real-world multicenter study.
LDH-driven lactic acidosis in hypoxic solid tumors: Mechanisms of metastatic transformation and therapeutic opportunities.
Emerging Frontiers in Neuro-Oncology: Insights into Extracellular Vesicle-Driven Tumor Mechanisms and Nanotherapeutic Strategies.
Editorial: The insights of multi-omics into the microenvironment after tumor metastasis: a paradigm shift in molecular targeting modeling and immunotherapy for advanced cancer patients.
Nomogram for survival prediction in metastatic differentiated thyroid cancer and survival comparison between systemic chemotherapy and local radiotherapy in high-risk patients.

Biomolecules. 2025 Dec 05. pii: 1696. [Epub ahead of print]15(12):

The Role of Extracellular Proteases and Extracellular Matrix Remodeling in the Pre-Metastatic Niche.

Gillian C Okura, Alamelu G Bharadwaj, David M Waisman.

  The premetastatic niche (PMN) represents a specialized microenvironment established in distant organs before the arrival of metastatic cells. This concept has fundamentally altered our understanding of cancer progression, shifting it from a random event-driven process to an orchestrated one. This review examines the critical role of extracellular proteases in PMN formation, focusing on matrix metalloproteinases (MMPs), serine proteases, and cysteine cathepsins that collectively orchestrate extracellular matrix remodeling, immune modulation, and vascular permeability changes essential for metastatic colonization. Key findings demonstrate that MMP9 and MMP2 facilitate basement membrane degradation and the recruitment of bone marrow-derived cells. At the same time, tissue inhibitor of metalloproteinase-1 (TIMP-1) promotes organ-specific hepatic PMN recruitment through neutrophil recruitment mechanisms. The plasminogen-plasmin system emerges as a master regulator through its broad-spectrum proteolytic activity and ability to activate downstream proteases, with S100A10-mediated plasmin generation providing mechanistic pathways for remote PMN conditioning. Neutrophil elastase and cathepsin G contribute to the degradation of anti-angiogenic proteins, thereby creating pro-metastatic microenvironments. These protease-mediated mechanisms represent the earliest interventional window in metastatic progression, offering therapeutic potential to prevent niche formation rather than treat established metastases. However, significant methodological challenges remain, including the need for organ-specific biomarkers, improved in vivo methods for measuring protease activity, and a better understanding of temporal PMN dynamics across different target organs.

Keywords:  S100A10; cathepsins; extracellular matrix remodeling; fibroblasts; matrix metalloproteases; myeloid-derived suppressor cells; neutrophils; plasmin; plasminogen; pre-metastatic niche; serine proteases; uPA; uPAR

DOI:  https://doi.org/10.3390/biom15121696
Int J Mol Sci. 2025 Dec 10. pii: 11893. [Epub ahead of print]26(24):

Microenvironmental and Molecular Pathways Driving Dormancy Escape in Bone Metastases.

Mohamad Bakir, Alhomam Dabaliz, Ahmad Dawalibi, Khalid S Mohammad.

  Bone metastases remain a leading cause of morbidity and mortality in patients with advanced breast, prostate, and lung cancers. A striking clinical feature of bone metastasis is the ability of disseminated tumor cells (DTCs) to persist in a dormant state for years or even decades before reawakening to drive overt disease. While the molecular and microenvironmental cues that induce and maintain dormancy have been increasingly studied, the mechanisms governing dormancy escape remain poorly defined yet are critical for preventing relapse. In this review, we synthesize emerging evidence on how the bone microenvironment orchestrates the transition of dormant tumor cells into proliferative lesions. We discuss how osteoclast-mediated bone resorption liberates growth factors such as TGF-β and IGF-1, fueling reactivation; how loss of osteoblast-mediated quiescence signals disrupts the endosteal niche; and how bone marrow adipocytes provide metabolic support through lipid transfer and adipokine secretion. We highlight the role of immune surveillance in maintaining dormancy and how immunosuppressive myeloid populations, regulatory T cells, and inflammatory triggers, such as neutrophil extracellular traps, promote escape. Additional emphasis is placed on extracellular matrix remodeling, mechanotransduction, angiogenic switching, and systemic factors, including aging, hormonal changes, and sympathetic nervous system activation. We also review epigenetic and metabolic reprogramming events within dormant cells that enable reactivation. Finally, we evaluate therapeutic strategies to sustain dormancy or prevent reawakening, including osteoclast-targeted therapies, immune-modulating approaches, and epigenetic or metabolic interventions. By integrating these insights, we identify key knowledge gaps and propose future directions to intercept dormancy escape and delay or prevent metastatic relapse in bone.

Keywords:  TGF-β signaling; bone marrow niche; bone metastases; dormancy escape; neutrophil extracellular trap; tumor dormancy

DOI:  https://doi.org/10.3390/ijms262411893
BMC Pulm Med. 2025 Dec 29. 25(1): 562

A novel tool to predict the probability of pulmonary metastasis in patients with primary osseous sacral/pelvic tumors: a large real-world multicenter study.

Zhenbang Zhou, Sanjun Chen, Zhangheng Huang, Binbin Yang, Zhen Zhao, Kai Chen, Peiling Dai.

   BACKGROUND: In patients with primary osseous sacral/pelvic tumors, once pulmonary metastasis has occurred, their prognosis is worrying. It is therefore essential to construct a novel tool to achieve accurate prediction of the probability of pulmonary metastasis from primary osseous sacral/pelvic tumors.
METHODS: This study retrospectively analyzed data from 407 patients with primary osseous sacral/pelvic tumors from the Surveillance, Epidemiology, and End Results database. Univariate and multivariate logistic regression analyses were used to identify risk factors. Construction of predictive models based on logistic regression algorithm in R software. The calibration, discrimination, and clinical utility of the models are validated in a validation cohort. The Kaplan-Meier survival curve and log-rank test were used to examine the pulmonary metastasis risk classification system for evaluation.
RESULTS: The total cohort was randomly divided into a training cohort (287 patients) and a validation cohort (120 patients). Five independent risk factors were identified to develop a nomogram model to predict the probability of pulmonary metastasis in patients. The area under the receiver operating characteristic curve (0.860 for the training cohort and 0.895 for the validation cohort) showed that the model showed satisfactory discrimination in both validation cohorts. The calibration curve showed a high predictive accuracy of the model and the Hosmer-Lemeshow test indicated a good model fit (p > 0.05). The decision curve analysis showed that the nomogram is clinically useful and can provide a net benefit to patients within certain limits.
CONCLUSION: We have successfully developed a nomogram and risk classification system to accurately predict the probability of pulmonary metastasis from primary osseous sacral/pelvic tumors.

Keywords:  Nomogram; Pulmonary metastasis; Risk factor; SEER database; Sacral/pelvic

DOI:  https://doi.org/10.1186/s12890-025-03766-y
Pathol Res Pract. 2025 Dec 25. pii: S0344-0338(25)00535-7. [Epub ahead of print]278 156342

LDH-driven lactic acidosis in hypoxic solid tumors: Mechanisms of metastatic transformation and therapeutic opportunities.

Priyanshu Kumar, Saumya Rastogi, Mandeep Kumar Arora, Lakhveer Singh.

  Lactic acidosis is a characteristic feature of solid hypoxic cancerous tumors, those that develop in the breast, colon, and prostate tissue. Even though extreme lactic acidosis is damaging to healthy cells, malignant tumors actually benefit from it in several different ways. Lactic acidosis in TME (TME) imparts resistance to chemotherapy and helps them from immune invasion. Lactic acidosis further benefits the tumor cells by inducing the formation of new blood vessels. Acidic tumour microenvironment (TME) provides very favourable pH conditions for activation of proteolytic enzymes like Matrix metalloproteinase (MMP-2/9), which helps the tumor cells invade into the nearby organs. Because aggressive hypoxic cancer cells have a high chance of metastasising to other organs, it is difficult to manage a tumor at this stage with chemotherapy. Stopping hypoxia-induced Lactate dehydrogenase (LDH) from working can prevent cancers from behaving aggressively. Restraining lactate circulation in the TME by inhibiting LDH and its transporters i.e Monocarboxylate transporters (MCT-1/2) would be a promising therapeutic strategy to prevent metastatic transformation of solid hypoxic tumors. Moreover, nanotechnology can be implicated in various ways to selectively kill the cancer cells. Whereas in some cancers, chemotherapeutic agents fail to activate, pH-sensitive nanoparticles can be designed to target such cancer cells. In the current review, we have highlighted the role and mechanisms of lactic acidosis to transform the benign tumours into more aggressive metastatic tumors. This review also offers fresh perspectives on the variety of LDH and MCT inhibitors currently undergoing clinical trials to act in the acidic TME.

Keywords:  Angiogenesis; Chemoresistance; Fatty acid synthesis; Hypoxia; Hypoxia-inducible factor-1α; Invasiveness; Lactate dehydrogenase; Lactic acidosis

DOI:  https://doi.org/10.1016/j.prp.2025.156342
Int J Mol Sci. 2025 Dec 07. pii: 11826. [Epub ahead of print]26(24):

Emerging Frontiers in Neuro-Oncology: Insights into Extracellular Vesicle-Driven Tumor Mechanisms and Nanotherapeutic Strategies.

Tommaso Colangelo, Anna Alessia Saponaro, Gianluigi Mazzoccoli, Gaetano Serviddio, Rosanna Villani.

  Brain tumors encompass a heterogeneous group of neoplasms, including primary and secondary metastatic lesions, with glioblastoma multiforme (GBM) representing the most aggressive primary malignancy. Despite advancements in surgical resection, radiotherapy, and chemotherapy, the prognosis for GBM remains poor due to its infiltrative nature, tumor heterogeneity and resistance mechanisms. Emerging diagnostic tools, such as liquid biopsies, and therapeutic strategies leveraging extracellular vesicles (EVs) are reshaping the field of neuro-oncology. EVs, lipid bilayer-enclosed particles secreted by cells, carry oncogenic cargo such as microRNAs and molecular chaperones, influencing tumor progression, immune evasion, and therapy resistance. Recent research highlights their potential as biomarkers for early diagnosis and vehicles for targeted drug delivery across the blood-brain barrier (BBB). EV-based nanotherapeutics show promise in improving treatment precision, reducing systemic toxicity, and advancing precision medicine in brain tumor management. However, challenges related to EV heterogeneity, cargo-loading efficiency, and large-scale production must be addressed to fully realize their therapeutic potential. This review explores the multifaceted roles of EVs in brain tumors, emphasizing their diagnostic, prognostic, and therapeutic applications.

Keywords:  extracellular vesicles (EVs); glioblastoma multiforme (GBM); microRNA; therapeutic vehicles; tumor aggressiveness

DOI:  https://doi.org/10.3390/ijms262411826
Front Oncol. 2025 ;15 1749178

Editorial: The insights of multi-omics into the microenvironment after tumor metastasis: a paradigm shift in molecular targeting modeling and immunotherapy for advanced cancer patients.

Xuejian Liu, Qi Wang, Yang Ma, Xinhua Xiao, Xue Zhao, Hailin Tang, Divya Gopinath, Chao Wang.



Keywords:  immunotherapy; metastasis; microenvironment; multi-omics; tumor

DOI:  https://doi.org/10.3389/fonc.2025.1749178
World J Surg Oncol. 2025 Dec 29. 23(1): 457

Nomogram for survival prediction in metastatic differentiated thyroid cancer and survival comparison between systemic chemotherapy and local radiotherapy in high-risk patients.

Jian Xu.

   BACKGROUND: Distant metastases are the leading cause of death for patients with differentiated thyroid cancer (DTC), and surgery and radioactive iodine (RAI) therapy are effective treatments for them. However, there remains a large proportion of patients with poor prognoses, and there exists no consensus on whether systemic chemotherapy or beam radiation should be administrated to improve their prognoses.
METHOD: The clinicopathology information of patients with metastatic DTC (mDTC) was retrospectively collected and analyzed. A nomogram was created to predict their prognosis and divided patients into high- and low-risk groups, and the external validation was performed.
RESULTS: The Cox regression showed that sex, age, metastatic sites, surgery, and radiotherapy were independent influencing factors affecting OS. Fine-gray competing risk analysis showed that age, T-stage, N-stage, metastatic sites, and radiotherapy were independent risk factors for TCSD. The nomogram we constructed proved to be effective and robust with high efficiency, with C-indexes of 0.785 (95% CI = 0.752-0.813) and 0.794 (95%CI = 0.766-0.831) on the train and test sets, respectively. mDTC patients were further classified into high- and low-risk groups based on the prediction of nomogram, those in the high-risk group had significantly worse OS and higher TCSD than those in the low-risk group (P < 0.001), and chemotherapy significantly improved OS and reduced TCSD for patients in the high-risk group, whereas local beam radiation did not provide any survival benefit. In the external validation dataset, the 1-, 3-, and 5-year AUC values of the model ranged from 0.833 to 0.873, which further proved the efficiency of our model.
CONCLUSION: This study developed an accurate prognostic model for patients with mDTC, which may be applicable in future clinical practice for prognosis and death prediction. For high-risk patients, as predicted by nomogram, systemic chemotherapy was the recommended therapy option for them.

Keywords:  Chemotherapy; Differentiated thyroid cancer; Distant metastases; Nomogram; Radioactive iodine; SEER

DOI:  https://doi.org/10.1186/s12957-025-04111-7