ABSTRACT
<p><b>OBJECTIVE</b>To explore the existence of vasculogenic mimicry (VM) in ovarian carcinoma and its correlationship with the clinicopathologic features and prognosis of the tumor.</p><p><b>METHODS</b>A total of 84 ovarian carcinoma cases were collected with complete clinical and prognostic data. CD31 immunohistochemistry and PAS special stain were used to investigate VM in the tumor tissue. Immunohistochemical staining of VEGF, MMP-2, MMP-9, E-cadherin, beta-catenin, and Vimentin were used to explore the pathogenesis of VM.</p><p><b>RESULTS</b>Totally 36 of 84 cases exhibited evidence of VM. FIGO classification, pathologic grades and histological types were significantly different between the VM and non-VM groups. Expression of VEGF, MMP-2, MMP-9, E-cadherin and beta-catenin were higher in the VM group than in the non-VM group. Kaplan-Meier survival curve analysis showed that cases of the VM group had a lower survival rate than that of the non-VM group (P = 0.04).</p><p><b>CONCLUSIONS</b>Vasculogenic mimicry exists in ovarian carcinoma. Ovarian carcinomas with a high grade malignancy have a high incidence of VM formation, a higher incidence of metastases and a lower survival rate. High expression of MMP-2 and MMP-9 may contribute to the formation of VM in the ovarian cancer.</p>
Subject(s)
Female , Humans , Middle Aged , Cadherins , Metabolism , Carcinoma, Endometrioid , Metabolism , Pathology , Cystadenocarcinoma, Mucinous , Metabolism , Pathology , Cystadenocarcinoma, Serous , Metabolism , Pathology , Matrix Metalloproteinase 2 , Metabolism , Matrix Metalloproteinase 9 , Metabolism , Neoplasm Metastasis , Neovascularization, Pathologic , Metabolism , Pathology , Ovarian Neoplasms , Metabolism , Pathology , Survival Rate , Vascular Endothelial Growth Factor A , Metabolism , beta Catenin , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the influence of different microenvironments on tumor microcirculation patterns and invasive capability.</p><p><b>METHODS</b>Melanoma B16 cells were injected into the peritoneal cavity and skeletal muscle of C57 mice synchronously. CK18 expression in melanoma was assessed to distinguish the malignant phenotype of tumors in the peritoneal cavity from that in the skeletal muscle. HIF-1alpha, MMP-2 and MMP-9 protein and mRNA expression were compared in the two microenvironments. Cells positive for each immunohistochemical stain and the vessels representative of each type of microcirculation pattern were evaluated in two microenvironments.</p><p><b>RESULTS</b>CK18 and HIF-1alpha expression in melanoma were significantly higher in the skeletal muscle than in the peritoneal cavity (t = 8.142, t = 3.645, P < 0.05). Compared with the peritoneal cavity, melanoma cells in the skeletal muscle overexpressed MMP-2 and MMP-9 (t = 4.916, t = 7.782, P < 0.05). Real time-PCR results also showed that MMP-2 and MMP-9 mRNA levels in melanoma were higher in the skeletal muscle than in the peritoneal cavity (t = 36.814, t = 26.025, P < 0.05). Vasculogenic mimicry channels and endothelium-dependent vessels were the major microcirculation patterns in the skeletal muscle and in the peritoneal cavity respectively.</p><p><b>CONCLUSIONS</b>Different microenvironments affect invasiveness and blood supply patterns of melanoma. Different microenvironment induced tumor cell secretion of more invasion-related proteins and affect invasiveness and blood supply patterns of melanoma.</p>
Subject(s)
Animals , Mice , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Hypoxia-Inducible Factor 1, alpha Subunit , Genetics , Matrix Metalloproteinase 2 , Genetics , Matrix Metalloproteinase 9 , Genetics , Melanoma , Genetics , Metabolism , Pathology , Mice, Inbred C57BL , Microcirculation , Muscle, Skeletal , Metabolism , Pathology , Neoplasm Invasiveness , Peritoneal Cavity , Pathology , Polymerase Chain Reaction , RNA, Messenger , Genetics , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the molecular mechanism of endostatin and doxycycline effect on melanoma growth.</p><p><b>METHODS</b>A B16 melanoma mice model was established by intracutaneous injection of B16 cell suspension. The mice were treated with endostatin, doxycycline, endostatin and doxycycline respectively, the control group received no treatment. A time course study of tumor volume was performed to observe the antitumor effect. The expression of matrix metalloproteinase (MMP-9), MMP-2, TIMP-2 were examined by immunohistochemistry staining.</p><p><b>RESULTS</b>Tumors in endostatin treatment group, doxycycline treatment group, endostatin and doxycycline treatment group grew slower than in the control group. The difference of the average tumor volume in the doxycycline group and control group, in the doxycycline with endostatin treatment group and control group were statistically different. The positive expression ratio of MMP-2, MMP-9, TIMP-2 in each treatment group were statistically different from their control groups (F = 12.79, F = 5.56, F = 4.64; P < 0.05).</p><p><b>CONCLUSION</b>Doxycycline and endostatin are able to inhibit the expression of MMPs and promote expression of TIMP, which ultimately inhibits the growth of B16 melonoma.</p>