Mingqing Song

Angiogenic role for glycodelin in tumorigenesis

Angiogenesis plays an important role in neovascularization in tumors. Glycodelin, a hormone-responsive protein, has been detected in tumors of reproductive organs and is found in high levels in the plasma of subjects with gynecological malignancies. Glycodelin is also found in the endothelial cells of the umbilical cord and in the blood vessels of tumors. In this study, we tested whether glycodelin-rich amniotic fluid and a synthetic peptide derived from the sequence of glycodelin peptide (Gp) might promote angiogenic response by examining the migration and tube formation in human umbilical cord vein endothelial cells (HUVECs). Increased migration and tube formation of HUVECs were found in the presence of amniotic fluid and Gp, and this increase was blocked by antibody to Gp and by an anti-vascular endothelial growth factor (VEGF) antibody, suggesting that the angiogenic effects of glycodelin might be mediated by VEGF. The results also showed that Gp significantly increased the release of VEGF protein and mRNA expression in HUVECs, RL-95 (human endometrial carcinoma cells), OVCAR-3 (human ovarian adenocarcinoma cells), EM42 (human endometrial epithelial cells), THP-1 (human monocyte), and MCF-7 and MDA-MB-231 (human breast adenocarcinoma cells) cell lines. VEGF receptor Fit-1 mRNA expression in HUVECs was also increased in the presence of Gp. These findings, together with the suggestion from the literature that glycodelin may have immunosuppressive properties, suggest that glycodelin might play an important role in neovascularization during embryogenesis and tumor development.

Atherosclerosis, Oxidation and Endometriosis

Endometriosis affects younger women of childbearing age. Atherosclerosis is considered as a disease of the old and increases with the ageing process. Both diseases are characterized by the increased presence of activated macrophages and associated increases in growth promoting activity and the production of inflammatory cytokines. In this review, we propose that oxidative stress and the presence of forms of oxidized low-density lipoprotein (LDL) might contribute to both Atherosclerosis and Endometriosis.

Increased Myeloperoxidase and Lipid Peroxide-Modified Protein in Gynecological Malignancies

Oxidative stress has been implicated in several diseases, including cancer. Oxidants induce oncogenes and their products associated with cell growth. Even though epidemiological studies implicate oxidants in promoting cancer, there is still a lack of in vivo evidence for the same. In this study, we measured the levels of myeloperoxidase (MPO), an enzyme associated with oxidation and autoantibodies to lipid peroxide-modified protein (LOOH-RSA), in the plasma of subjects with gynecological cancers. The gynecological cancer subjects (n = 201) had higher plasma MPO and LOOH-RSA levels compared with control subjects (n = 60). Immunohistochemical analysis of tissues revealed that immunostaining for MPO and LOOH-RSA was higher in cancer tissues compared with controls. The staining was specific to cell types and not ubiquitously present. Neutrophils, monocytes/macrophages, and natural killer cells have been proposed to play a role in cancer promotion and progression. This study proposes a role for oxidative stress and especially MPO in cancer.

Presence of endometrial epithelial cells in the peritoneal cavity and the mesothelial inflammatory response

OBJECTIVE To determine the contribution of endometrial cells in the development of endometriosis. Specifically the response of the mesothelium to endometrial cells in the production of monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), and IL-8 was studied. DESIGN In vitro study. SETTING University Research Laboratory. PATIENT(S) None. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Cellular MCP-1, IL-6 secretion and MCP-1, and IL-6 and IL-8 messenger RNA expression were evaluated by ELISA and reverse transcription-polymerase chain reaction (RT-PCR) assay. RESULT(S) The mesothelial cells produced more MCP-1 and IL-6 than endometrial epithelial and stromal cells. Mesothelial cells cultured in the presence of endometrial epithelial cells produced even greater levels of MCP-1 and IL-6 than those cultured in the presence of stromal cells or cultured alone. The MCP-1, IL-6, and IL-8 mRNA expression also increased when mesothelial cells were co-cultured with endometrial epithelial cells. CONCLUSION(S) The results suggest that endometrial epithelial cells may be important in evoking the inflammatory reaction in the peritoneal cavity during retrograde menstruation and that mesothelial cells may play an important role in the chemotaxis of monocytes and in the inflammatory process during the development of endometriosis.