High cancer cell death in syngeneic tumors developed in host mice deficient for the stromelysin-3 matrix metalloproteinase

Matrix metalloproteinases (MMPs) are extracellular enzymes. Some of them ar e known to be involved in tumor development and/or progression. Several cel lular functions have been proposed for MMPs during malignant processes. Not ably, they may be involved in tissue-remodeling processes through their abi lity to digest matrix components or to participate in tumor neoangiogenesis and, subsequently, in cancer cell proliferation, One of these MMPs, strome lysin-3 (ST3/MMP11), although devoid of enzymatic activity against the matr ix components, is associated with human tumor progression and poor patient clinical outcome, Using several in vivo experimental models, it has been de monstrated that ST3 expression by the fibroblastic cells surrounding malign ant epithelial cells promotes tumorigenesis in a paracrine manner, The pres ent study was devoted to the identification of the cellular function underl ying this ST3-induced tumor promotion using a syngeneic tumorigenesis model in mice. Our results show that ST3 exhibits a new and unexpected role for a MMP, because ST3-increased tumorigenesis does not result from increased n eoangiogenesis or cancer cell proliferation but from decreased cancer cell death through apoptosis and necrosis, Thus. during malignancy, the cellular function of ST3 is to favor cancer fell survival in the stromal environmen t.