Blood Coagulation Factor Fibrinogen in Tumor Pathogenesis of Central Nervous System B-Cell Lymphoma

Autor: Justin P. Chan, James L. Rubenstein, Mario Merlini, Andrew S. Mendiola, Hua-Xin Gao, Katerina Akassoglou, Jae K. Ryu
Rok vydání: 2021
Předmět:
0301 basic medicine
Male
Pathology
Lymphoma
Nude
Fibrinogen
Medical and Health Sciences
Pathogenesis
Central Nervous System Neoplasms
Mice
0302 clinical medicine
Cerebrospinal fluid
immune system diseases
hemic and lymphatic diseases
2.1 Biological and endogenous factors
Lymphocytes
Aetiology
B-cell lymphoma
Cancer
Regular Article
Hematology
medicine.anatomical_structure
Coagulation
Neurological
medicine.symptom
medicine.drug
Biotechnology
medicine.medical_specialty
Lymphoma
B-Cell
Central nervous system
Mice
Nude
Inflammation
Pathology and Forensic Medicine
03 medical and health sciences
Rare Diseases
Clinical Research
medicine
Cell Adhesion
Animals
Humans
business.industry
Animal
B-Cell
Neurosciences
Biological Transport
medicine.disease
Brain Disorders
Brain Cancer
Disease Models
Animal
030104 developmental biology
Disease Models
business
030217 neurology & neurosurgery
Zdroj: The American journal of pathology, vol 191, iss 3
Am J Pathol
Popis: Central nervous system (CNS) lymphoma is an extranodal non-Hodgkin B-cell lymphoma characterized by malignant lymph tissue arising in the brain or spinal cord, associated with inflammation and blood-brain barrier (BBB) disruption. Although BBB disruption is known to occur in patients with CNS lymphoma, a direct link between these two has not been shown. Herein, abundant deposition of the blood coagulation protein fibrinogen around B-cell lymphoma was detected in CNS lymphoma patients and in the CNS parenchyma in an orthotopic mouse model. Functional enrichment analysis of unbiased cerebrospinal fluid proteomics of CNS B-cell lymphoma patients showed that coagulation protein networks were highly connected with tumor-associated biological signaling pathways. Invivo two-photon imaging demonstrated that lymphoma growth was associated with BBB disruption, and invitro experiments identified a role for fibrinogen in promoting lymphoma cell adhesion. Overall, these results identify perivascular lymphoma clustering at sites of fibrinogen deposition, and suggest that fibrinogen may be a target for pharmacologic intervention in metastatic B-cell lymphoma associated with BBB disruption.
Databáze: OpenAIRE
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