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Matrix metalloproteinases: roles in cancer and metastasis
1Dept of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Barbara.fingleton@vanderbilt.edu
Abstract:
The matrix metalloproteinase (MMP) family of extracellular proteinases play roles in normal physiological processes as well as in multiple disease settings including cancer. The link between MMP activity and cancer was considered strong enough to warrant considerable investment in pharmacological inhibitors of MMPs as a potential therapeutic modality, however, multiple large-scale clinical trials have all failed to reach their primary endpoints. This has led us to re-evaluate our thinking with respect to MMPs in cancer and shown that, most importantly, we need to understand the range of functions of these enzymes before we can effectively modulate them. The MMPs contribute to every stage of tumor progression, not just the later stages as was originally assumed. Additionally, through processing of their various substrates, MMP activity can have both pro- and anti-tumorigenic functions, thus their broad inhibition is likely to have unwanted consequences in some settings. Interactions between MMPs and proteinases of other classes are another important aspect of tumor biology and understanding these interactions is also necessary for development of effective therapeutic strategies. The aim of this article is to summarize recent findings in these areas and put them in the context of our growing understanding of how MMPs function in cancer development and progression.
Insights
Matrix metalloproteinases (MMPs) are crucial in cancer progression, impacting all stages. Understanding their diverse roles is key to developing effective cancer therapies, as broad inhibition has shown limited success.
Area of Science:
- Biochemistry
- Oncology
- Molecular Biology
Background:
- Matrix metalloproteinases (MMPs) are extracellular proteinases involved in physiological processes and diseases like cancer.
- Extensive research invested in MMP inhibitors for cancer therapy yielded disappointing clinical trial results.
- This necessitates a re-evaluation of MMP functions in cancer, moving beyond earlier assumptions.
Purpose of the Study:
- To summarize recent findings on MMP functions in cancer development and progression.
- To contextualize these findings within the broader understanding of MMPs' roles.
- To highlight the importance of understanding MMPs' diverse functions and interactions for therapeutic strategies.
Main Methods:
- Review of recent scientific literature on matrix metalloproteinases in cancer.
- Analysis of MMPs' roles across all stages of tumor progression.
- Examination of MMPs' substrate processing and their dual pro- and anti-tumorigenic effects.
- Investigation of interactions between MMPs and other proteinases in tumor biology.
Main Results:
- MMPs contribute to every stage of tumor progression, not solely later stages.
- MMP activity can exert both pro-tumorigenic and anti-tumorigenic effects depending on substrate processing.
- Broad inhibition of MMPs may lead to adverse outcomes in certain cancer contexts.
- Interactions between MMPs and other proteinases are critical in tumor biology.
Conclusions:
- A comprehensive understanding of MMPs' multifaceted roles is essential for effective cancer therapy.
- Targeting MMPs requires a nuanced approach, considering their diverse functions and interactions.
- Future therapeutic strategies should account for the complex biology of MMPs in cancer progression.
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