Funding outcome

Our recent work on breast cancer provides a new understanding of how this disease progresses and spreads to other parts of the body. We established a novel concept in which the breast tumor causes inflammation in the surrounding fat tissue of the breast. This fat tissue responds by producing a protein that increases the production of a compound called lysophosphatidate (LPA). This sets up a vicious cycle of inflammation. LPA stimulates the release of more inflammatory compounds, which in turn caused the production of more LPA. This inflammatory cycle promotes the growth of the breast tumor and its spread to other parts of the body. The present work provides a new approach to breaking this inflammatory cycle. LPA is degraded by enzymes called lipid phosphate phosphatase-1 (LPP1) and (LPP3). These enzymes block the ability of LPA to activate cells. However, the expressions of LPP1 and LPP3 are decreased in cancer cells, which makes them extremely sensitive to the effects of LPA. We showed that restoring the expressions of LPP1 blocks the growth of breast tumors and their spread by about 80%. By contrast, another member of the LPP family, LPP2, is increased in cancer cells. This increases the division of the cancer cells. We now provide preliminary evidence that the increased expression of LPP2 in cancer cells could also be responsible for decreasing the activities of LPP1 and LPP3. The proposal project will investigate how LPP2 has this effect. We will also decrease the expression of LPP2 in breast cancer cells and test whether this will block tumor growth and spread. If so, we will identify LPP2 as a new target that can be used to treat breast cancer patients.