Phospholipase D, MMP-2 and TIMP-2 Expression in the Human Colorectal Cancer

ABSTRACT

BACKGROUND: Tumor invason and metastasis are the major causes of morbidity and death for cancer patients. Metastatic spread depends critically upon the invasiveness of the tumor cells, i.e., their ability to breach basement membrane by profusely secreting specific proteolytic enzymes such as MMP-2. TIMP-2 has a high affinity for progelatinase A and will form a 11 complex with either the latent or activated forms of the enzyme and has inhibitory activity against MMP-2. Laminin induced activation of Phospholipase D (PLD) and consequent generation of phosphatidic acid are involved in a signal propagation pathway leading to induction of MMP-2 in metastatic HT 1080 fibrosarcoma cells. We also studied a expression of PLD, MMP-2 and TIMP-2 in colorectal adenocarcinoma. METHODS: Colorectal adenocarcinomas from 13 patients in our hospital were studied for immunohistochemical expression of PLD, MMP-2, and TIMP-2 to assess their diagnostic and prognostic importance as well as relation between PLD and MMP-2. RESULTS: 1) Expression of PLD-2 was detected in 77% of the cases in colorectal adenocarcinomas. 2) MMP-2 expression was significantly associated with the presence of lymph-node metastasis, with moderated to strong expression present in 100% of the cases compared with 28.6% of the non-metastatic cases (P-value=0.017). 3) For colorectal adenocarcinomas, a strong correlation between PLD and MMP-2 expression was detected (P-value=0.008). CONCLUSION: PLD-2 can be used as a potential marker for malignant disease in colorectal adenocarcinomas. MMP-2 expression was significantly associated with the presence of lymph-nodemetastasis. A strong correlation between PLD and MMP-2 expression was also detected in colorectal carcinoma.