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Studies On The Expression Of Slit2/Robo1 In Tumor Angiogenesis

Posted on:2006-04-12Degree:MasterType:Thesis
Country:ChinaCandidate:N ZhangFull Text:PDF
GTID:2144360155464063Subject:Cell biology
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Angiogenesis involves the sprouting, branching, and differential growth of blood vessels to form the more mature-appearing vascular patterns seen in the adult organisms. It is of crucial importance in a variety of physiological and pathological conditions. Except for female reproductive cycles, angiogenesis in adult is largely controlled by pathological conditions, such as wound healing and tumor growth. Moreover, the obligatory requirement of angiogenesis for the growth and metastasis of cancers is now well recognized. For example, the growth of solid tumors requires concomitant expansion of vascular networks to maintain the blood supply of oxygen and nutrients. Also, some scientific researchers have found some important angiogenic molecules, like vascular growth factors (VEGFs), fibroblast growth factors (FGFs), etc. However, the molecular and cellular mechanisms regulating tumor angiogenesis are still under studies. Slit is secreted protein known to function through the Roundabout (Robo) receptor as a chemorepellent in axon guidance and neuronal migration, and as an inhibitor in leukocyte chemotaxis.This paper is mainly about a series of researches on the expression of Slit2 and Robol in tumor angiogenesis with the immunohistochemical staining.In this paper, the xenografted tumor growth mouse model was founded by injecting tumor cells subcutaneously into athymic nude mice. The results showed: using the immunohistochemical staining with Slit2 and Robol poly-antibodies, I found Slit2 and Robol present in A375 (a human malignant melanoma cell line) cells and vascular endothelial cells respectively. Also, in Western-Blotting, Slit2 is expressed by A375 cells and Robol is expressed by HUVECs (Human Umbilical Vein Endothelial Cells). Interestingly, specific neutralization of Robol reduced the tumor mass and the microvessel density of A375 cells in vivo. In addition, the expression of Slit2 and Robol was also found in some human tumor samples (as colon melanoma) through the immunohistochemical staining. These findings provide strong evidence to theinvestigation of the angiogenic function of Slit-Robo signaling in tumor angiogenesis. What's more, the results indicate the possible effectiveness of blocking Slit-Robo signaling pathway in treating cancers.
Keywords/Search Tags:tumor angiogenesis, Slit-Robo signaling, vascular endothelial cells, cancer cells
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