Extracellular matrix proteases - cytokine regulation role in cancer and pregnancy
Bor-Ching Sheu1, Wen-Chun Chang1, Chieh-Yang Cheng1, Peng-Hui Wang2, Shiming Lin3, Su-Cheng Huang1
1
Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University, Taipei, Taiwan, 2Department of Obstetrics and Gynecology, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan, 3Center of Photoelectronics, College of Medicine, National Taiwan University, Taipei, Taiwan
TABLE OF CONTENTS
- 1. Abstract
- 2. Introduction
- 3. ECM Proteases, inhibitors & cancer
- 3.1. MMPs functions in promoting cancer development
- 3.2. ADAMs share the similar function with MMPs in cancer development
- 3.3. TIMPs function in suppressing cancer development
- 3.4. Other MMP inhibitors antagonize MMPs functions
- 4. Effects of MMPs and cytokines mutual regulation in cancer development
- 4.1. MMPs regulate cytokine induction in cancer development
- 4.2. The impact of cytokine induction on MMPs expression in cancers
- 4.3. The impact of chemokine induction on MMPs expression in cancers
- 5. Effects of MMPs and cytokines mutual regulation in pregnancy
- 5.1. MMPs and cytokines mutual regulation during embryo implantation
- 5.2. MMPs and cytokines mutual regulation during parturition
- 5.3. MMPs and cytokines mutual dysregulation during abortion
- 5.4. MMPs and cytokines mutual dysregulation during preterm delivery
- 5.5. Therapeutic approaches of MMPs in abnormal pregnancy and endometriosis
- 6. Therapeutic approaches about MMPs in cancer
- 6.1. Synthetic MMP inhibitors
- 6.2. TIMPs act as endogenous inhibitors
- 6.3. Therapeutic approaches aim at MMPs expression rather than MMPs enzymatic activity
- 6.4. Therapeutic approaches focus to the cancer microenvironment
- 6.5. Therapeutic approaches target to the MMP gene expression
- 7. Perspective
- 8. Acknowledgments
- 9. References
1. ABSTRACT
The extracellular matrix proteases act in diverse physiological and pathological processes involving tumor growth, angiogenesis, and pregnancy through the cleavage of extracellular matrix (ECM) and non-matrix proteinaceous substrates. Matrix metalloproteinases (MMPs) constitute a main family among the ECM proteases. Endogenous tissue inhibitors of metalloproteinases (TIMPs), as one kind of MMPs inhibitors (MMPIs), reduce the excessive proteolytic ECM degradation by MMPs. The balance between MMPs and TIMPs plays a major role in cancer tumorigenesis, angiogenesis, as well as embryo implantation and trophoblastic invasion during pregnancy. A variety of literature concerns the correlated changes in MMPs and MMPIs during the formation of cancer and pregnancy-related complications. Importantly, MMPs and TIMPs may act as regulators of signaling pathways through the cleavage of non-matrix substrates, including cytokines, chemokines, and growth factors. In this review, we concentrate on mutual interactions between ECM proteases and cytokines during cancer development and pregnancy. The current knowledge in the field of identified ECM proteases will be contributive to the innovative therapeutic intervention in both cancer and pregnancy-related processes.
