The Extracellular Matrix in Glioblastomas: A Glance at Its Structural Modifications in Shaping the Tumoral Microenvironment—A Systematic Review

Abstract

Background and aim: While many components of the ECM have been isolated and characterized, its modifications in the specific setting of GBMs have only been recently explored in the literature. The aim of this paper is to provide a systematic review on the topic and to assess the ECM’s role in shaping tumoral development. Methods: An online literature search was launched on PubMed/Medline and Scopus using the research string “((Extracellular matrix OR ECM OR matrix receptor OR matrix proteome) AND (glioblastoma OR GBM) AND (tumor invasion OR tumor infiltration))”, and a systematic review was conducted in accordance with the PRISMA-P guidelines. Results: The search of the literature yielded a total of 693 results. The duplicate records were then removed (n = 13), and the records were excluded via a title and abstract screening; 137 studies were found to be relevant to our research question and were assessed for eligibility. Upon a full-text review, 59 articles were finally included and were summarized as follows based on their focus: (1) proteoglycans; (2) fibrillary proteins, which were further subdivided into the three subcategories of collagen, fibronectin, and laminins; (3) glycoproteins; (4) degradative enzymes; (5) physical forces; (6) and glioma cell and microglia migratory and infiltrative patterns. Conclusions: Our systematic review demonstrates that the ECM should not be regarded anymore as a passive scaffold statically contributing to mechanical support in normal and pathological brain tissue but as an active player in tumor-related activity.

Identification of established and novel extracellular matrix components in glioblastoma as targets for angiogenesis and prognosis

“…Tumor-instructed stromal cells have differential effects on tumor cell proliferation and migration in vitro, indicating a reciprocal crosstalk between neoplastic and non-neoplastic cells, such as EC (Bougnaud et al, 2016;Testa et al, 2022). The composition of ECM and its stored-signaling factors also influence the behavior of GBM cells and GBM stromal cells, affecting GBM angiogenesis, infiltration and aggressiveness (Alves et al, 2011a;Dinevska et al, 2023;Marino et al, 2023). Understanding the complex interplay between the ECM, GBM cells and EC in the tumor angiogenesis and aggressiveness is crucial for finding new biomarkers to improve patient outcomes and for the development of targeted therapies.…”

HIF-1α-mediated LAMC1 expression is an unfavorable predictor of prognosis for glioma patients: Evidence from pan-cancer analysis and validation experiments

“…Although an early report mentioned a relationship between LAMC1 and hypoxia [33], this study clari ed the regulatory relationship between HIF-1α and LAMC1 expression, which expands our understanding of the molecular mechanism of ECM remodeling in the hypoxic microenvironment of malignant tumors. As a major factor involved in tumorigenesis, progression, and the tumor microenvironment, the ECM has become a therapeutic target and potential prognostic marker for gliomas [34]. By considering LAMC1 as target, Kulkarni et al found that LAMC1 and laminin family members are critical for H-1 parvovirus cell attachment and entry, and can be used as biomarkers to facilitate identifying sensitivity to H-1 parvovirus oncolytic therapy [35].…”

HIF-1α-mediated LAMC1 overexpression is an unfavorable predictor of prognosis for glioma patients: evidence from pan-cancer analysis and validation experiments

“…As a major factor involved in tumorigenesis, progression, and the tumor microenvironment, the ECM has become a therapeutic target and potential prognostic marker for gliomas [ 36 ]. By considering LAMC1 as target, Kulkarni et al found that LAMC1 and laminin family members are critical for H-1 parvovirus cell attachment and entry, and can be used as biomarkers to facilitate identifying sensitivity to H-1 parvovirus oncolytic therapy [ 37 ].…”