Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
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MMPs are zinc-dependent endopeptidases that are involved in proteolysis of extracellular matrix in both physiological and pathological processes including cancer. MMPs are involved at all stages of tumor progression, including tumor growth, angiogenesis, and metastasis. We recently showed that overexpression of Lefty in cancer cells restrains tumor growth. Here, we show that small forms of Lefty are generated by MMP2 (gelatinase A) mediated cleavage. In turn, these forms of Lefty strongly inhibit the autocatalytic, gelatinolytic and caseinolytic activities of MMP2 in vitro. We show that a short synthesized form of Lefty peptide (CASDGALVP) inhibits gelatinolytic and caseinolytic activities of MMP2 in vitro and inhibits tumor growth in vivo. Together, these findings show that lefty peptides are a new class of gelatinase A inhibitors that restrain tumor growth.