angiogenin and Mouth-Neoplasms

Squamous cell carcinoma is often associated with the deletion or mutation of zinc finger protein 750 (ZNF750), its deletion or mutation is associated with squamous epithelial malignant biological characteristics. The present study is to explore the mechanism of ZNF750 to suppress the tumor malignant process by regulation tumor microenvironment.. To evaluate the changes of tumor microenvironment in oral squamous cells carcinoma cell line CAL-27 cell, the expression of angiogenin, vascular endothelial growth factor (VEGF), prolyl hydroxylase 2 (PHD2), G protein signal regulated protein 5 (RGS5), integrin A5 (ITGA5), integrin B1 (ITGB1) and CD44 were detected by Western-blot. The changes of platelet derived growth factor (PDGFB) and tumor vascular marker CD105 (Endoglin) mRNA were estimated by qPCR. The effect of over-expressed ZNF750 on cell viability and lateral migration capacity was investigated by CCK-8 and cell scratch assay in three oral squamous cells carcinoma.. ZNF750 could effectively inhibit the protein or mRNA expression of angiogenin, VEGF, RGS5 and CD105, repressed the cell adhesion molecules ITGA5, ITGB1 and CD44, but up-regulate the protein or mRNA expression of PHD2 and PDGFB. The cell viability and lateral migration ability of three oral squamous cells carcinoma were reduced by over-expression of ZNF750.. ZNF750 could modulate the tumor vascular microenvironment to inhibit the oral squamous cells carcinoma malignant progression.

Topics: Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; Cell Survival; Genes, Tumor Suppressor; HEK293 Cells; Humans; Mouth Neoplasms; Neovascularization, Pathologic; Ribonuclease, Pancreatic; Transcription Factors; Tumor Microenvironment; Tumor Suppressor Proteins; Vascular Endothelial Growth Factor A

Angiogenin undergoes nuclear translocation and stimulates ribosomal RNA transcription in both endothelial and cancer cells. Consequently, angiogenin has a dual effect on cancer progression by inducing both angiogenesis and cancer cell proliferation. The aim of this study was to assess whether neamine, a blocker of nuclear translocation of angiogenin, possesses antitumor activity toward oral cancer.. The antitumor effect of neamine on oral cancer cells was examined both in vitro and in vivo.. Neamine inhibited the proliferation of HSC-2, but not that of SAS oral cancer cells in vitro. Treatment with neamine effectively inhibited growth of HSC-2 and SAS cell xenografts in athymic mice. Neamine treatment resulted in a significant decrease in tumor angiogenesis, accompanied by a decrease in angiogenin- and proliferating cell nuclear antigen-positive cancer cells, especially of HSC-2 tumors.. Neamine effectively inhibits oral cancer progression through inhibition of tumor angiogenesis. Neamine also directly inhibits proliferation of certain types of oral cancer cells. Therefore, neamine has potential as a lead compound for oral cancer therapy.

Topics: Angiogenesis Inducing Agents; Animals; Cell Line, Tumor; Cell Proliferation; Disease Progression; Framycetin; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Mice; Mice, Nude; Mouth Neoplasms; Neovascularization, Pathologic; Protein Transport; Ribonuclease, Pancreatic; Xenograft Model Antitumor Assays

Angiogenin (ANG) is a prominent angiogenic factor that has been shown to have a dual effect on tumor progression by inducing both angiogenesis and cancer cell proliferation through stimulating ribosomal RNA transcription in both endothelial cells and cancer cells. In the present study, we investigated the expression profiles of ANG and vascular endothelial growth factor (VEGF) in oral cancer and their correlation with hypoxia and evaluated the possible value of ANG as a therapeutic target for oral cancer.. Immunohistochemistry (IHC), ELISA, real-time RT-PCR and Western blotting were used to examine the expression of ANG, VEGF, and hypoxia-inducible factor 1α (HIF-1α) in oral squamous cell carcinoma (OSCC) specimens and human OSCC cell lines. In order to examine the role of ANG, we knocked down ANG expression in HSC-2 cells by means of plasmid-mediated RNA interference.. IHC showed that the expression of ANG was significantly correlated with that of HIF-1α in 50 OSCC specimens (P = 0.031). However, no significant correlation between VEGF and HIF-1α expression was found (P = 0.243). Consistently, ANG secretion increased under hypoxia in all of the 10 OSCC cell lines tested; and a significant increase was observed in 6 of them. In contrast, there was no noticeable increase in VEGF secretion under hypoxia in any of these cell lines. In HSC-2 and SAS OSCC cells, the increase in ANG mRNA expression correlated very well with that of HIF-1α protein expression after hypoxia onset. However, no noticeable increase in VEGF mRNA expression was observed even after 12 h of hypoxia. Down-regulation of ANG expression in HSC-2 cells highly expressing and secreting VEGF inhibited ribosome biogenesis, cell proliferation, tumor angiogenesis, and xenograft growth in athymic mice.. These results suggest that ANG is up-regulated in the hypoxic environment of oral cancers and that its inhibition can have a therapeutic implication.

Topics: Animals; Blotting, Western; Carcinoma, Squamous Cell; Cell Hypoxia; Enzyme-Linked Immunosorbent Assay; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Mice; Mice, Nude; Mouth Neoplasms; Real-Time Polymerase Chain Reaction; Ribonuclease, Pancreatic; Vascular Endothelial Growth Factor A

We report a case of lymphangioma involving oral mucosa and mandible of an elderly female. The surgical and radiological examinations indicated that the lymphangioma was mainly distributed in the labial mucosa tissue, but had gradually extended into the periosteum and intrabony space of mandible. Immunohistochemical staining was also performed using antiseras of alpha-smooth muscle actin (alpha-SMA), von Willebrand factor (vWF), angiogenin, vascular endothelial growth factor (VEGF), and proliferating cell nuclear antigen (PCNA) to elucidate the pathogenetic implications of the intraosseous lymphangioma. The present case of lymphangioma showed strong immunohistochemical reactivity of angiogenin and vWF, while it showed weak reactions of VEGF and PCNA. The immunostaining of alpha-SMA disclosed an abnormally thinned and discontinuous smooth muscle layer in the lymphatics. Both the X-rays and histological examination showed that the lymphangioma lesion was gradually extending into the adjacent osteoporotic marrow space of mandible. Therefore, we believe that the present case of intraosseous lymphangioma, which showed the harmatomatous growth of the lymphatics into the marrow space of mandible, is closely related to osteoporotic changes of old age.

Topics: Actins; Aged; Angiogenesis Inducing Agents; Bone Marrow; Endothelial Growth Factors; Female; Hamartoma; Humans; Immunohistochemistry; Lymphangioma; Lymphatic Diseases; Lymphoid Tissue; Lymphokines; Mandibular Diseases; Mandibular Neoplasms; Mouth Mucosa; Mouth Neoplasms; Muscle, Smooth; Neoplasm Invasiveness; Neoplasm Proteins; Osteoporosis; Proliferating Cell Nuclear Antigen; Protein Isoforms; Ribonuclease, Pancreatic; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; von Willebrand Factor