期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/ijms22073403
关键词
ovarian cancer; proteolysis; proteases; extracellular matrix; mesothelial cells; peritoneum; mesenchymal; matrix metalloproteinase
资金
- National Institutes of Health (NIH)/National Institute of Aging (NIA) [F99 AG068527]
- NIH/National Cancer Institute (NCI) [RO1 CA109545, UO1 CA236797]
- Leo and Ann Albert Charitable Trust
Proteases, particularly those of the matrix metalloproteinase family, play a crucial role in ovarian cancer progression and metastasis by enhancing migratory ability, ECM breakdown, and tumor support system development. Upregulation of certain proteases influences angiogenesis for tumor growth and development of metastatic implants.
Proteases play a crucial role in the progression and metastasis of ovarian cancer. Pericellular protein degradation and fragmentation along with remodeling of the extracellular matrix (ECM) is accomplished by numerous proteases that are present in the ovarian tumor microenvironment. Several proteolytic processes have been linked to cancer progression, particularly those facilitated by the matrix metalloproteinase (MMP) family. These proteases have been linked to enhanced migratory ability, extracellular matrix breakdown, and development of support systems for tumors. Several studies have reported the direct involvement of MMPs with ovarian cancer, as well as their mechanisms of action in the tumor microenvironment. MMPs play a key role in upregulating transcription factors, as well as the breakdown of structural proteins like collagen. Proteolytic mechanisms have been shown to enhance the ability of ovarian cancer cells to migrate and adhere to secondary sites allowing for efficient metastasis. Furthermore, angiogenesis for tumor growth and development of metastatic implants is influenced by upregulation of certain proteases, including MMPs. While proteases are produced normally in vivo, they can be upregulated by cancer-associated mutations, tumor-microenvironment interaction, stress-induced catecholamine production, and age-related pathologies. This review outlines the important role of proteases throughout ovarian cancer progression and metastasis.
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