Collectively, these results suggest a novel mechanism in which macrophage-secreted MMP-9 cleaves HB-EGF from the macrophage surface, leading to activated EGFR in OVCA433 and up-regulation of MMP-9, creating a positive feedback loop for HB-EGF bioavailability and increased proliferation in tumor cells (Figure 7D). Here, HBEGF is linked to neoplasm.