Plasmin and Plasminogen System in the Tumor Microenvironment: Implications for Cancer Diagnosis, Prognosis, and Therapy

The tumor microenvironment (TME) is now being widely accepted as the key contributor to a range of processes involved in cancer progression from tumor growth to metastasis and chemoresistance. The extracellular matrix (ECM) and the proteases that mediate the remodeling of the ECM form an integral pa...

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Bibliographic Details
Published in:Cancers 2021-04, Vol.13 (8), p.1838
Main Authors: Bharadwaj, Alamelu G, Holloway, Ryan W, Miller, Victoria A, Waisman, David M
Format: Article
Language:English
Subjects:
Adipocytes
Angiogenesis
Blood clots
Calcium-binding protein
Cancer
Cell activation
Cell adhesion & migration
Chemoresistance
Extracellular matrix
Fibroblasts
Gene expression
Hematology
Medical prognosis
Metastases
Metastasis
Plasmin
Plasminogen activator inhibitors
Plasminogen receptors
Proteins
Review
Reviews
S100 protein
Serine
Serine proteinase
Solid tumors
Stromal cells
t-Plasminogen activator
Tumor cells
Tumor microenvironment
U-Plasminogen activator
Wound healing
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Summary:The tumor microenvironment (TME) is now being widely accepted as the key contributor to a range of processes involved in cancer progression from tumor growth to metastasis and chemoresistance. The extracellular matrix (ECM) and the proteases that mediate the remodeling of the ECM form an integral part of the TME. Plasmin is a broad-spectrum, highly potent, serine protease whose activation from its precursor plasminogen is tightly regulated by the activators (uPA, uPAR, and tPA), the inhibitors (PAI-1, PAI-2), and plasminogen receptors. Collectively, this system is called the plasminogen activation system. The expression of the components of the plasminogen activation system by malignant cells and the surrounding stromal cells modulates the TME resulting in sustained cancer progression signals. In this review, we provide a detailed discussion of the roles of plasminogen activation system in tumor growth, invasion, metastasis, and chemoresistance with specific emphasis on their role in the TME. We particularly review the recent highlights of the plasminogen receptor S100A10 (p11), which is a pivotal component of the plasminogen activation system.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13081838