0000000001195082
AUTHOR
Rebeca Burgos-panadero
Integrating the Tumor Microenvironment into Cancer Therapy
© 2020 by the authors.
Una visión integral del cáncer (I). Microambiente tumoral: estudio, clasificación y reprogramación
Resumen El grupo de enfermedades al que nos referimos como «cancer» comparte una estructura biologica conformada por un ecosistema complejo, donde se han alterado las relaciones intercelulares, los campos de informacion, el desarrollo y la funcion tisular. Mas alla de las alteraciones geneticas de la celula tumoral, la demostracion de un ecosistema alterado, con sus interconexiones a nivel sistemico, abre una nueva perspectiva de la biologia y del comportamiento del cancer. Diversas facetas del tumor, su morfologia, clasificacion, agresividad clinica, pronostico y respuesta al tratamiento aparecen ahora bajo una vision integral que ofrece un nuevo horizonte de estudio, investigacion y manej…
Additional file 4: of Vitronectin as a molecular player of the tumor microenvironment in neuroblastoma
Table S3. Growth conditions of NB human cell lines. (DOCX 14 kb)
Unraveling the extracellular matrix-tumor cell interactions to aid better targeted therapies for neuroblastoma
Treatment in children with high-risk neuroblastoma remains largely unsuccessful due to the development of metastases and drug resistance. The biological complexity of these tumors and their microenvironment represent one of the many challenges to face. Matrix glycoproteins such as vitronectin act as bridge elements between extracellular matrix and tumor cells and can promote tumor cell spreading. In this study, we established through a clinical cohort and preclinical models that the interaction of vitronectin and its ligands, such as αv integrins, are related to the stiffness of the extracellular matrix in high-risk neuroblastoma. These marked alterations found in the matrix led us to speci…
Una visión integral del cáncer (II). Campos de estudio y biomarcadores emergentes
Pathology and clinical oncology work hand in hand so that techniques and treatments, biomarkers and antibodies share the common goal of identifying integral new treatment regimens that are more effective and less aggressive. Evidence shows how tissue mechanics affect carcinogenesis and that tumor heterogeneity depends on metabolic stromal alteration and the Warburg effect of malignant cells, regulated directly by PD-1, becoming a target for immunotherapy. Proliferation and apoptosis depend on mitochondrial dysfunction in tumor cells, determining the grade of chemo/radio-resistance. The status of intestinal microbiota regulates immune response, tumor microenvironment structure and oncologic …
The topology of vitronectin: A complementary feature for neuroblastoma risk classification based on computer‐aided detection
Tumors are complex networks of constantly interacting elements: tumor cells, stromal cells, immune and stem cells, blood/lympathic vessels, nerve fibers and extracellular matrix components. These elements can influence their microenvironment through mechanical and physical signals to promote tumor cell growth. To get a better understanding of tumor biology, cooperation between multidisciplinary fields is needed. Diverse mathematic computations and algorithms have been designed to find prognostic targets and enhance diagnostic assessment. In this work, we use computational digital tools to study the topology of vitronectin, a glycoprotein of the extracellular matrix. Vitronectin is linked to…
Una visión integral del cáncer (III). Evaluación de nuevos biomarcadores y posibilidades de intervención
We propose a comprehensive approach to oncological disease, based on a systemic consideration of biology, health and disease. Our two previous review articles focused on tumour microenvironment and the discovery of new biomarkers; here we discuss the practical application of these principles to pathology, through the identification, evaluation and quantitative analysis of new prognostic and predictive factors (Immunoscore, TIME). We also consider the clinical use of promising, better tolerated treatments, such as immunotherapy. The integrative pathologist now has access to the latest improved oncology stratification tools designed to identify effective treatment strategies, based on the nat…
The tumour microenvironment as an integrated framework to understand cancer biology
Cancer cells all share the feature of being immersed in a complex environment with altered cell-cell/cell-extracellular element communication, physicochemical information, and tissue functions. The so-called tumour microenvironment (TME) is becoming recognised as a key factor in the genesis, progression and treatment of cancer lesions. Beyond genetic mutations, the existence of a malignant microenvironment forms the basis for a new perspective in cancer biology where connections at the system level are fundamental. From this standpoint, different aspects of tumour lesions such as morphology, aggressiveness, prognosis and treatment response can be considered under an integrated vision, givin…
Additional file 2: of Vitronectin as a molecular player of the tumor microenvironment in neuroblastoma
Table S2. Description of the image analysis process. (DOCX 15 kb)
Digital Image Analysis Applied to Tumor Cell Proliferation, Aggressiveness, and Migration-Related Protein Synthesis in Neuroblastoma 3D Models
Patient-derived cancer 3D models are a promising tool that will revolutionize personalized cancer therapy but that require previous knowledge of optimal cell growth conditions and the most advantageous parameters to evaluate biomimetic relevance and monitor therapy efficacy. This study aims to establish general guidelines on 3D model characterization phenomena, focusing on neuroblastoma. We generated gelatin-based scaffolds with different stiffness and performed SK-N-BE(2) and SH-SY5Y aggressive neuroblastoma cell cultures, also performing co-cultures with mouse stromal Schwann cell line (SW10). Model characterization by digital image analysis at different time points revealed that cell pro…
Additional file 1: of Vitronectin as a molecular player of the tumor microenvironment in neuroblastoma
Table S1. Descriptors and median values of vitronectin and nuclei morphometric variables in the present cohort. (DOCX 19 kb)
The oral KIF11 inhibitor 4SC‐205 exhibits antitumor activity and potentiates standard and targeted therapies in primary and metastatic neuroblastoma models
Inhibidor de KIF11; Terapias dirigidas; Metástasis Inhibidor de KIF11; Teràpies dirigides; Metàstasi KIF11 inhibitor; Targeted therapies; Metastasis In summary, our study provides a rationale for the future therapeutic integration in clinical trials of 4SC-205, an structurally distinct oral KIF11 inhibitor that shows potent antitumor activity in multiple preclinical neuroblastoma models and sensitizes neuroblastoma cells to standard chemotherapy and specific neuroblastoma-targeted therapies. The financial support for this research was provided by Instituto de Salud Calos III (PI20/00530 to Miguel F. Segura; PI20/01107 to Rosa Noguera; PI17/02248 and CPII18/00027 to Anna Santamaria; PI19/013…
Vitronectin as a molecular player of the tumor microenvironment in neuroblastoma
Background Vitronectin is a multifunctional glycoprotein known in several human tumors for its adhesive role in processes such as cell growth, angiogenesis and metastasis. In this study, we examined vitronectin expression in neuroblastoma to investigate whether this molecule takes part in cell-cell or cell-extracellular matrix interactions that may confer mechanical properties to promote tumor aggressiveness. Methods We used immunohistochemistry and image analysis tools to characterize vitronectin expression and to test its prognostic value in 91 neuroblastoma patients. To better understand the effect of vitronectin, we studied its in vitro expression using commercial neuroblastoma cell lin…
Additional file 3 of Vitronectin as a molecular player of the tumor microenvironment in neuroblastoma
Figure S1. Examples of how these applications work in vitronectin samples. A. Liver sample image immunostained for vitronectin (VN) without segmentation. B. Image of liver control sample segmentation with the DensitoQuant module (Pannoramic viewer software). C. Image of liver control sample segmentation with Image Pro-Plus software. D. Primary neuroblastoma (NB) sample immunostained for VN without segmentation. E. Image of NB sample segmentation with the DensitoQuant module (Pannoramic viewer software). F. Image of NB sample segmentation with Image Pro-Plus software. (ZIP 8306 kb)