Cyclooxygenase-two (COX-2) modulates proliferation in aggressive fibromatosis (desmoid tumor)

Aggressive fibromatosis is a locally invasive soft tissue lesion. Seventy-f ive per cent of cases harbor a somatic mutation in either the APC or beta - catenin genes, resulting in beta -catenin protein stabilization, Cyclooxyge nase-2 (COX-2) is an enzyme involved in prostaglandin synthesis that modula tes the formation of colonic neoplasia, especially in cases due to mutation s resulting in beta -catenin stabilization, Human aggressive fibromatoses a nd lesions from the Apc+/Apc1638N mouse (a murine model for Ape-driven fibr omatosis) demonstrated elevated COX-2 levels. COX-2 blockade either by the selective agent DFU or by non-selective COX blocking agents results in redu ced proliferation in human tumor cell cultures. Breeding mice with Cox-2-/- mice resulted in no difference in number of aggressive fibromatoses formed , but in a smaller tumor size, while there was a decrease in number of GI l esions by 50%. Mice fed various COX blocking agents also showed a decline i n tumor size. COX-2 expression was regulated by tcf-dependent transcription in this lesion, COX-2 partially regulates proliferation due to beta -caten in stabilization in aggressive fibromatosis, Although COX blockade alone do es not cause tumor regression, this data suggests that it may have a role a s an adjuvant therapy to slow tumor growth in this lesion.