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Emerging roles of plasma gelsolin in tumorigenesis and modulating the tumor microenvironment
Chih-Hsiung Hsieh1, Yi-Ching Wang1,2
1Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Abstract:
The protein expression of gelsolin, an actin scavenger controlling cytoskeletal remodeling, cell morphology, differentiation, movement, and apoptosis, has been found to be significantly decreased in several pathological conditions including neurodegenerative diseases, inflammatory disorders, and cancers. Its extracellular isoform, called plasma gelsolin (pGSN), is one of the most abundant plasma proteins in the circulation, and has emerged as a novel diagnostic biomarker for early disease detection. Current evidence reveals that gelsolin can function as either an oncoprotein or a tumor suppressor depending on the carcinoma type. Interestingly, recent studies have shown that pGSN is also involved in immunomodulation, revealing the multifunctional roles of pGSN in tumor progression. In this review, we discuss the current knowledge focusing on the roles of gelsolin in inflammation and wound healing, cancers, and tumor microenvironment. Future prospects of pGSN related studies and clinical application are also addressed.
Insights
Gelsolin protein levels decrease in disease. Its plasma form (pGSN) is a biomarker for early detection and plays roles in inflammation, cancer, and immunity, offering future clinical applications.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Gelsolin is a key regulator of the actin cytoskeleton, influencing cell functions like movement and apoptosis.
- Decreased gelsolin expression is observed in various pathologies, including neurodegenerative diseases, inflammation, and cancers.
- Plasma gelsolin (pGSN), an extracellular isoform, is abundant in circulation and shows potential as an early disease diagnostic biomarker.
Purpose of the Study:
- To review the multifaceted roles of gelsolin, particularly plasma gelsolin (pGSN), in inflammation, wound healing, and cancer.
- To explore the dual function of gelsolin as an oncoprotein or tumor suppressor depending on cancer type.
- To discuss the immunomodulatory functions of pGSN and its impact on tumor progression.
Main Methods:
- Literature review of current research on gelsolin and plasma gelsolin.
- Analysis of studies investigating gelsolin's involvement in cellular processes and disease pathology.
- Synthesis of evidence regarding pGSN's roles in inflammation, immunity, and cancer.
Main Results:
- Gelsolin's expression is significantly reduced in several pathological conditions.
- pGSN acts as a potential diagnostic biomarker for early disease detection.
- Gelsolin exhibits context-dependent roles in cancer, functioning as both an oncoprotein and a tumor suppressor.
- pGSN is implicated in immunomodulation and influences tumor microenvironment dynamics.
Conclusions:
- Gelsolin and its plasma form, pGSN, are critical players in inflammation, wound healing, and cancer.
- pGSN holds significant promise as a diagnostic biomarker and therapeutic target.
- Further research into pGSN's functions could lead to novel clinical applications in disease management.
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