Relationship Between MMP-2,9 Expression And VEGF/N-Ras/ERK Signaling Pathway In Leukemia

Angiogenesis is defined as the process of formatting a new capillary network . This capillary network comes from prior existential blood vessels by germination or un - germination style. Series studies prove that angiogenesis is important to tumors growth and metastasis. The blood malignant tumor also have angiogenesis phenomena. The tumor's angiogenesis is relate to a series of growth factors, which stimulate endothelial cells to growth and excite the capillary network's generation.The Matrix metalloproteinase ( MMP) - 2,9 are important enzymes that breakdown the extra cellular matrix in the procession of solid tumor invasion and metastasis Now they are reported to be involved in hematopoiesis and some of the hematopoietic malignancies. Vascular endothelial growth factor ( VEGF) is a specific mitogen to vascular endothelium. The VEGF family consists of VEGF (1,2,3,4) and VEGFR - 1 (flt - 1) , VEGFR-2 (flk-1), VEGFR-3 (flt -4) , VEGFR -4. The recipients of VEGF family members are all tyrosine ki-nase recipients, ras was an oncogene, which can make the normal cells convert to cancer cell. In mammal animals,ras family has three members H-ras, K -ras, N- ras. The Ras family members' code producers are all molecular weight 21KD protein,so call p21 protein. In blood system, N -ras is the most important. ERK( extra cellular signal - regulated kinase) has ERK1 ,ERK2 two members. Moreover, the recent research has demonstrated a close relation between MMP -2,9 and VEGF/N - ras/pERK . in order to investigate the mechanism of leukemia cells malignant transformation and infiltration, and thus provide therapy basis for preventing and treating hematopoietic malignancies, our study exam-ined the expression of VEGF^N - Ras^ Perk ^ MMP -2,9 in bone marrow cells of untreated hematopoietic malignancies cells.Materials and method1. The study objects are 60 AML bone marrow specimens, 20 complete remission AML patients'bone marrow specimens,30 ALL bone marrow specimens, 15 CML bone marrow specimens, 20 contrasts bone marrow specimens.2. Bone marrow fluids are retreated with heparinization. Bone marrow is extracted mono - nucleus cell by Ficoll density gradient centrifugation. After the number cells with light microscope. The cells, smeared by cell smearing centrifugal machine. Specimens conservative in -40X1. The samples are incubated in room temperature 30 min. Detecting MMP - 2,9^ VEGFA N - Ras^ pERK by immunohistochemistry method. By light microscope number positive cells,and calculate the positive ratio. The statistics analysis by SPSS 11.0.Results1. The expression of MMP - 2: (1) preliminary diagnosis AML^ ALL^CML expression rate are significantly higher than contrast bundle ( P <0.05). Complete remission(CR) AML and contrast bundle's MMP -2 expression rate have not significant difference ( P > 0.05). Preliminary diagnosis AML MMP - 2 expression rate is significantly higher than complete remission AML contrast bundle (P < 0. 05). (2) The positive rate of MMP -2 in untreated ALL group and untreated AML ( M4 + M5 ) group are significantly higher than that in untreated AML (non M4 + M5) group(p <0. 05) and there is no significant difference between the former two groups ( p > 0. 05 ) .2. The expression of MMP -9: (1 preliminary diagnosis AML^ ALL^CML expression rate are significantly higher than contrast bundle( P <0. 05) . ( CR) AML and contrast bundles MMP -9 expression rate have not significant difference (P >0.05 ) . Preliminary diagnosis AML MMP - 9 expression rate is significantly higher than (CR) AML contrast bundle (P < 0. 05). (2) The positiverate of MMP - 9 in untreated ALL group and untreated AML ( M4 + M5) group are significantly higher than that in untreated AML ( nonM4 + M5 ) group (p < 0. 05) and there is no significant difference between the former two groups (p > 0.05).3. The expression of VEGF;preliminary diagnosis AML^ CML VEGF expression rate are significantly higher than contrast bundle ( p < 0. 05). ALL, complete remission AML and contrast bundle's VEGF expression rate have not significant difference (P>0.05). Preliminary diagnosis AML VEGF expression rate is significantly higher than complete remission AML contrast bundle ( P < 0. 05).4. The expression of N - Ras: preliminary diagnosis AML, CML N - Ras expression rate are significantly higher than contrast bundle (P <0. 05) ALL, complete remission AML and contrast bundled N — Ras expression rate have not significant difference ( P > 0. 05 ). Preliminary diagnosis AML N - Ras expression rate is significantly than higher than complete remission AML contrast bun-dle(P<0.05).5. The expression of pERK: preliminary diagnosis AML, CML pERK expression rate are significantly higher than contrast bundle (P < 0. 05). ALL, complete remission AML and contrast bundle's pERK expression rate have not significant difference (P >0.05). Preliminary diagnosis AML pERK expression rate is significantly higher than complete remission AML contrast bundle(P <0. 05).Conclusion1. Preliminary diagnosis AML^CML MMP -2,9N VEGF^N - Ras, pERK expression rate significantly higher than contrast bundle (P < 0. 05). complete remission AML and contrast bundle's, MMP -2,9^VEGF^N -pERK expression rate have not significant difference ( P > 0. 05). Preliminary diagnosis AML VEGF^N - Ras^ pERK expression rate is significantly higher than complete remission AML contrast bundle ( P <0.05).2. MMP -2 and MMP -9 over express in untreated acute leukemia groupand the positive rates are significant higher than completely remission stage of a-cute leukemia group. It shows that the over expression of MMP -2 and MMP -9 were a early event in acute leukemia MMPs may play an important role during leukemic cells malignant transformation and infiltration. (2) MMP - 2 and MMP - 9 over express in he positive rates are significant higher than that in CR stage of AL group. MMPs can enhance the degradation of ECM and induce leukemic cells invasion and infiltration(§)The positive rates of MMP - 2 and MMP - 9 in ALL and AML ( M4 + M5 ) group are significant higher than those in AML ( non M4 + M5) group. It shows that MMPs were closely associated with ALL and M4, M5 invasion.3. N - Ras, pERK, VEGF MMP -2,9 have close correlation( p <0. 01).4. VEGF correlated to Ras/MAPK signal conduction pass.