MDNews - Greater Boston

Cellular Double Agent: enzyme responsible for Cancer Metastasis Also Signals Immune response By Michael Ferguson MatrIX MetalloProteInaSeS (MMPS) Were long thought to ProMote BreaSt cancer groWth, But neW reSearch InDIcateS a SuBgrouP WIthIn thIS FaMIlY oF enZYMeS MaY alSo act aS a Beacon to the IMMune SYSteM, DIrectIng It Where to attacK. C aNCer Cells ProduCe MMPs, which encourage a number of behaviors, including angiogenesis, apoptosis, immune surveillance, metastasis and tumor growth. When first generation MMP-inhibiting trials failed, researchers began to reconceptualize the enzyme's role in cancer's cellular tactics, says Dylan Edwards, PhD, School of Biological Sciences, University of East Anglia. "It became clear that some of these enzymes actually seem to inhibit malignancy rather than promote it," Edwards says. "Essentially, they are 'anti-targets.'" But this seeming clarity was still obscured by the fact that MMPs do play a role in cancer growth and metastasis. Edwards and his team further investigated individual components within the MMP family, focusing specifically on MMP-8 — an enzyme that has demonstrated ability to stunt tumor cell growth. The team's research was recently published in the Journal of Biological Chemistry. "In this paper, we looked at the effects of production of MMP-8 by breast cancer cells, showing that it leads to an up-regulation of the expression of both interleukin-6 [IL-6] and interleukin-8 [IL-8], which are inflammatory mediators that mostly act to promote malignant behavior," Edwards explains. "So we have this paradoxical question: Why does an anti-metastatic enzyme induce tumor promoting factors?" like a bat signal The group's paper suggests that IL-6 and IL-8 production is precisely what alerts the immune system to the presence of cancer and initiates an attack response. "We're currently testing preclinical models in vivo," Edwards says. "The bottom line is that we think that by 10 | Greater Boston MD News ■ mdNews.Com activating the production of IL-6 and IL-8, the tumor cells effectively kick the host's immune system into action; hence, MMP-8 gives off a 'find me' signal." Possible early-stage utility Any process that subverts cancer's natural defense to elude attack from its host's immune system can possibly be used to develop more effective treatment regimens. Immunotherapies are being widely tested for a broad range of cancers, and Edwards explains that MMP-8 could join these therapies as an early-stage treatment option. "More selective MMP-8 sparing inhibitors that are being developed by various pharmaceutical companies might have better success as therapies," Edwards says. "However, it has to be recognized that MMP inhibition is most effective at early stages of tumor progression. So, such inhibitors are unlikely to be effective as single-agents for cancer therapy, but they may well have powerful actions, particularly in combination with anti-angiogenic drugs." ■

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