Significance of monocyte chemotactic protein-1 and thymidine phosphorylase in angiogenesis of human cardiac myxoma.

Angiogenesis is indispensable to tumor development and proliferation. The aim of this study was to investigate whether the expression of monocyte chemotactic protein-1 (MCP-1) and of thymidine phosphorylase (TP) correlates with the angiogenesis and clinicopathologic features in cardiac myxoma. Paraffin-embedded specimens of 17 resected cardiac myxomas were immunohistochemically stained for MCP-1, CC chemokine receptor-2 (CCR-2), TP, CD31, and CD68. Correlations among MCP-1 expression, TP expression, microvessel count (determined by CD31 staining), macrophage count (determined by CD68 staining), and the clinicopathologic features of the patients were analyzed statistically. Immunohistochemical analysis revealed that MCP-1 and TP were expressed in myxoma cells, as well as in stromal cells such as infiltrating cells, fibroblast-like cells and endothelial cells. CCR-2 was abundantly expressed in stromal infiltrating cells in all myxomas and occasionally in the endothelial cells. In the tumor stroma, the major source of MCP-1, TP and CCR-2 was macrophages, and the sites of positive staining for MCP-1, TP and CCR-2 matched in most of the myxomas. Statistical analysis revealed that the proportions of MCP-1-positive myxoma and stromal cells, and TP-positive myxoma and stromal cells significantly correlated with increased microvessel count. The proportions of MCP-1-positive myxoma and stromal cells significantly correlated with the proportion of TP-positive stromal cells. The mean microvessel count in myxomas with both high tumor and high stromal MCP-1 or TP expression was significantly higher than that in myxomas with low tumor and low stromal MCP-1 or TP expression. Small tumors (< or =55 mm in diameter) exhibited high MCP-1 or TP expression, and the microvessel count in small tumors was significantly higher than in large myxomas. Although the difference was not significant, myxomas with both high tumor and high stromal MCP-1 expression had a higher macrophage count than other myxomas. These results indicate that in cardiac myxoma, MCP-1 and TP may be regarded as important angiogenic signals accompanying growth.

[1]  K. Matsushima,et al.  Human MCAF Gene Transfer Enhances the Metastatic Capacity of a Mouse Cachectic Adenocarcinoma Cell Line in Vivo , 2004, Pharmaceutical Research.

[2]  Y. Oike,et al.  Increased expression of monocyte chemoattractant protein-1 in atherectomy specimens from patients with restenosis after percutaneous transluminal coronary angioplasty. , 2002, Circulation journal : official journal of the Japanese Circulation Society.

[3]  S. Hokimoto,et al.  Plasma monocyte chemoattractant protein-1 antigen levels and the risk of restenosis after coronary stent implantation. , 2001, Japanese circulation journal.

[4]  S. Hokimoto,et al.  Increased plasma antigen levels of monocyte chemoattractant protein-1 in patients with restenosis after percutaneous transluminal coronary angioplasty. , 2000, Japanese circulation journal.

[5]  H. Saji,et al.  Significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis, and survival in human breast cancer. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[6]  J. Ward,et al.  Human endothelial cells express CCR2 and respond to MCP-1: direct role of MCP-1 in angiogenesis and tumor progression. , 2000, Blood.

[7]  M. Isobe,et al.  Expression of vascular endothelial growth factor and angiogenesis in cardiac myxoma: a study of fifteen patients. , 2000, The Journal of thoracic and cardiovascular surgery.

[8]  H. Watanabe,et al.  Immunohistochemical expression of thymidine phosphorylase/platelet-derived endothelial cell growth factor in squamous cell carcinoma of the esophagus. , 1999, Hepato-gastroenterology.

[9]  宮寺 和孝 Role of thymidine phosphorylase activity in the angiogenic effect of platelet-derived endothelial cell growth factor/thymidine phosphorylase , 1999 .

[10]  T. Shono,et al.  Involvement of interleukin-8, vascular endothelial growth factor, and basic fibroblast growth factor in tumor necrosis factor alpha-dependent angiogenesis , 1997, Molecular and cellular biology.

[11]  Yûsaku Okada,et al.  Expression of platelet‐derived endothelial cell growth factor in bladder carcinoma , 1997, Cancer.

[12]  L. Ellis,et al.  Platelet-derived endothelial cell growth factor in human colon cancer angiogenesis: role of infiltrating cells. , 1996, Journal of the National Cancer Institute.

[13]  Y. Chung,et al.  Thymidine phosphorylase/platelet-derived endothelial cell growth factor expression associated with hepatic metastasis in gastric carcinoma. , 1996, British Journal of Cancer.

[14]  S. Akiba,et al.  Expression of Thymidine Phosphorylase in Human Gastric Carcinoma , 1996, Japanese journal of cancer research : Gann.

[15]  J. Kuratsu,et al.  Expression of monocyte chemoattractant protein-1 in meningioma. , 1995, Journal of neurosurgery.

[16]  G. Stamp,et al.  The detection and localization of monocyte chemoattractant protein-1 (MCP-1) in human ovarian cancer. , 1995, The Journal of clinical investigation.

[17]  H. Ishitsuka,et al.  Expression of platelet‐derived endothelial cell growth factor/thymidine phosphorylase in human breast cancer , 1995, International journal of cancer.

[18]  Y. Chung,et al.  Tumor angiogenesis as a predictor of recurrence in gastric carcinoma. , 1995, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  A. Harris,et al.  Cytokine networks in solid human tumors: regulation of angiogenesis , 1994, Journal of leukocyte biology.

[20]  L. Pusztai,et al.  Expression of tumour necrosis factor alpha and its receptors in carcinoma of the breast. , 1994, British Journal of Cancer.

[21]  T. Furukawa,et al.  Angiogenic activity of enzymes , 1994, Nature.

[22]  R. Strieter,et al.  Interleukin-8 as a macrophage-derived mediator of angiogenesis. , 1992, Science.

[23]  D. Graves,et al.  Expression of monocyte chemotactic protein-1 in human melanoma in vivo. , 1992, The American journal of pathology.

[24]  A. Yoshimura,et al.  Angiogenic factor , 1992, Nature.

[25]  D. Steinberg,et al.  Expression of monocyte chemoattractant protein 1 in macrophage-rich areas of human and rabbit atherosclerotic lesions. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Leonard,et al.  Cytokine-activated human endothelial cells synthesize and secrete a monocyte chemoattractant, MCP-1/JE. , 1990, The American journal of pathology.

[27]  P. Morméde,et al.  Immunoreactive fibroblast growth factor in cells of peritoneal exudate suggests its identity with macrophage-derived growth factor. , 1985, Biochemical and biophysical research communications.

[28]  J. Folkman Tumor angiogenesis. , 1985, Advances in cancer research.