PAPPA and neoplasm: A role for PAPPA promoting cancer is supported by several lines of evidence; PAPPA null mice display a reduced incidence of spontaneous tumor formation as compared to age matched controls [37], high levels of PAPPA have been associated with progression in other tumor types [11, 12, 16, 37, 38] and Pan et al demonstrated that secreted, rather than cell-associated PAPPA, was associated with cancer growth and progression [39].