Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential

Recent epidemiologic studies have shown a 40-50% reduction in mortality from colorectal cancer in individuals who take nonsteroidal antiinflammatory drugs on a regular basis compared with those not taking these agents, One property shared bg all of these drugs is their ability to inhibit cyclooxygenase (COY), a keg enzyme in the conversion of arachidonic acid to prostaglandins. Two isoforms of COX have been characterized, COX-I and COX-2, COX-2 is expressed at high levels in intestinal tumors in humans and rodents, Human colon cancer tells (Caco-2) were permanently transfected with a COX-2 expression vector or the identical vector lacking the COX-2 insert, The Caco-2 cells, which constitutively expressed COX-2, acquired increased invasiveness compared with the parental Caco-2 cells or the vector transfected control cells. Biochemical changes associated with this phenotypic change included activation of metalloproteinase-2 and increased RNA levels for the membrane-type metalloproteinase, increased invasiveness and prostaglandin production were reversed by treatment with sulindac sulfide, a known COX inhibitor, These studies demonstrate that constitutive expression of COX-2 can lead to phenotypic changes that alter the metastatic potential of colorectal cancer cells.