Related Experiment Video
Updated: Mar 30, 2026
Author Spotlight: Developing Parmodulins to Target Protease-Activated Receptors for Inflammation Control
Published on: May 24, 2024
Original insights on thrombospondin-1-related antireceptor strategies in cancer
Albin Jeanne1, Christophe Schneider2, Laurent Martiny2
1Laboratoire SiRMa, UFR Sciences Exactes et Naturelles, Université de Reims Champagne-Ardenne Reims, France ; CNRS, Matrice Extracellulaire et Dynamique Cellulaire, UMR 7369 Reims, France ; SATT Nord Lille, France.
Abstract:
Thrombospondin-1 (TSP-1) is a large matricellular glycoprotein known to be overexpressed within tumor stroma in several cancer types. While mainly considered as an endogenous angiogenesis inhibitor, TSP-1 exhibits multifaceted functionalities in a tumor context depending both on TSP-1 concentration as well as differential receptor expression by cancer cells and on tumor-associated stromal cells. Besides, the complex modular structure of TSP-1 along with the wide variety of its soluble ligands and membrane receptors considerably increases the complexity of therapeutically targeting interactions involving TSP-1 ligation of cell-surface receptors. Despite the pleiotropic nature of TSP-1, many different antireceptor strategies have been developed giving promising results in preclinical models. However, transition to clinical trials often led to nuanced outcomes mainly due to frequent severe adverse effects. In this review, we will first expose the intricate and even sometimes opposite effects of TSP-1-related signaling on tumor progression by paying particular attention to modulation of angiogenesis and tumor immunity. Then, we will provide an overview of current developments and prospects by focusing particularly on the cell-surface molecules CD47 and CD36 that function as TSP-1 receptors; including antibody-based approaches, therapeutic gene modulation and the use of peptidomimetics. Finally, we will discuss original approaches specifically targeting TSP-1 domains, as well as innovative combination strategies with a view to producing an overall anticancer response.
Insights
Thrombospondin-1 (TSP-1) impacts tumor growth through complex signaling. Targeting TSP-1 receptors like CD47 and CD36 offers therapeutic potential, but clinical translation requires overcoming adverse effects.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Thrombospondin-1 (TSP-1) is a matricellular glycoprotein overexpressed in tumor stroma.
- TSP-1 has dual roles in cancer, influencing angiogenesis and immunity based on concentration and receptor interactions.
- Targeting TSP-1 is complex due to its modular structure and diverse ligands/receptors.
Purpose of the Study:
- To elucidate the intricate and often opposing effects of TSP-1 signaling on tumor progression, angiogenesis, and immunity.
- To review current therapeutic strategies targeting TSP-1, focusing on CD47 and CD36 receptors.
- To discuss novel approaches including antibody-based therapies, gene modulation, peptidomimetics, TSP-1 domain targeting, and combination strategies.
Main Methods:
- Review of existing literature on Thrombospondin-1 (TSP-1) function in cancer.
- Analysis of preclinical and clinical data for TSP-1-targeting therapies.
- Focus on cell-surface receptors CD47 and CD36 as key mediators of TSP-1 effects.
Main Results:
- TSP-1 exhibits pleiotropic effects on tumor progression, impacting angiogenesis and immune responses.
- Preclinical anti-receptor strategies show promise, but clinical trials face challenges with severe adverse effects.
- CD47 and CD36 are critical TSP-1 receptors, with various therapeutic modalities under investigation.
Conclusions:
- Understanding TSP-1's complex roles is crucial for developing effective cancer therapies.
- Targeting TSP-1 receptors and domains, alongside combination strategies, holds promise for improved anticancer responses.
- Further research is needed to optimize therapeutic strategies and mitigate adverse effects for successful clinical translation.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:27Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include:
01:17Intracellular Signaling Affects Focal Adhesions
Some...
01:15Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
02:30Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
01:25Selectins