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The Expression of Sema6D and Its Receptor PlexinA1 in Gastric Carcinoma and Their Clinicopathologic Significance

Author: ZhaoXiangYang
Tutor: ChenLin
School: PLA Postgraduate Medical School
Course: General Surgery
Keywords: Sema6D PlexinA1 Tumor cell proliferation Angiogenesis Gastric cancer
CLC: R735.2
Type: PhD thesis
Year: 2008
Downloads: 73
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Abstract


Primary gastric carcinoma is one of the most common malignant tumors in China. Invasion and metastasis are the main cause for the death of cancer patients. On the other hand, invasion and metastasis of malignant tumors are closely related with angiogenesis of tumor tissue and tumor cell proliferation. The semaphorins family is characterized by a phylogenetically conserved sema domain in the extracellular region, and family has been subdivided into eight groups, which play crucial roles in formation of nervous systems, embryogenesis, angiogenesis, immunoreaction, and carcinogenesis . Semaphorin 6D is a novel member of class 6 semaphorin gene, mapped on the chromosome 2, and it is grouped into five isoforms through different splicing. The research show semaphorin 6D inhibit axonal extension of NGF-differentiated PC12 cells and to collapse growth cones of chick DRG and rat hippocampal neurons. A wealth of knowledge has been generated in the past decade about the fact that blood vessels and nerves share common mechanisms in choosing and following specific paths to reach their respective targets. The vascular and nervous systems have several striking anatomical similarities. They both consist of a highly complex and precisely branched network, reaching the most distant cells in the organism. The specialization of the arterio-venous blood vessel system to transport oxygen and remove carbon dioxide resembles the organization of the nervous system to transmit, via afferent sensory and efferent motor neurons, electrical impulses bidirectionally. Moreover, both blood vessels and nerves consist of two cell types, endothelial/mural cells, and neurons/glia, respectively. In addition to sharing morphological features, both the vascular and nervous systems develop by following similar sequences of developmental events. As in the vascular system, the first step in the nervous system development involves the differentiation of progenitors into neurons with the subsequent formation of central structures, such as the neural tube and dorsal root ganglia. From these, the neurons sprout axons to reach distal targets in a highly ordered and stereotyped manner, thus establishing an intricately interconnected peripheral neural network. Certain nerves follow the path of blood vessels and are closely aligned with branching vessels, raising the question whether the molecular signals, governing branching of these two systems, are related and interdependent. Sema6D was observed to attract or inhibit epithelial cells migration depending on different special regions through different receptor complex in cardiac morphogenesis of chick embryos. PlexinA1 is a large transmembrane protein that is a major receptor for multiple classes of Somaphorins, either alone or in combination with neuropilins. In present, some research show PlexinA1 is major receptor of Sema6D. However, little is known about the founctions of sema6D and PlexinA1. Furthermore, the founctions of semaphorin 6D and PlexinA1 in carcinogenesis remains unrevealed. Therefore, It is important to explore the expression in gastric carcinoma and their relationship with tumor angiogenesis and proliferation.We detected Sema6D and PlexinA1 protein expressions of Sema6D by RT-PCR and Western blotting in 20 cases of gastric carcinoma and corresponding normal gastric mucosa. Sema6D, PlexinA1, Ki-67 expression and microvessel density (MVD) in 50 cases of gastric carcinoma and 20 cases of normal gastric mucosa were detected by immunohistochemistry. The results showed that the mRNA and protein expression of Sema6D in gastric carcinoma was significantly higher than that in normal gastric mucosa ( 0.24±0.06 vs 0.19±0.07 , P = 0.013<0.05 and 0.45±0.16vs0.29±0.08, P=0.0001<0.01), and MVD within tumor tissues increased significantly with Sema6D mRNA and protein expression (r =0.6367, P=0.003< 0.01) and Sema6D protein expression (r =0.5759, P=0.008<0.01), and The MVD of the Sema6D positive staining group (25.18±3.57) was significantly higher than that of the negative group (18.97±1.47) (P < 0.01). Proliferation index of tumor cells within tumor tissues were positively correlated with Sema6D mRNA expression (r =0.6258, P=0.003<0.01) and Sema6D protein expression (r =0.5996, P=0.005< 0.01). The proliferation index of the Sema6D positive staining group(572.50±112.12) was significantly higher than that of the negative group (340.82±103.07) (P < 0.01). The mRNA and protein expression of PlexinA1 in gastric carcinoma was significantly higher than that in normal gastric mucosa (0.71±0.37vs0.60±0.25, P=0.0299< 0.05,and 0.47±0.16vs0.21±0.08, P=0.0000<0.01) , and MVD within tumor tissues increased significantly with PlexinA1 mRNA expression (r =0.8736, P<0.01) and PlexinA1 protein expression ( r =0.7286, P<0.01), and The MVD of the PlexinA1 positive staining group (25.25±3.93) was significantly higher than that of the negative group (19.56±1.75) (P < 0.01). Proliferation index of tumor cells within tumor tissues were positively correlated with PlexinA1 mRNA expression (r =0.5420, P=0.014 <0.01) and PlexinA1 protein expression ( r =0.5024, P=0.024 < 0.05). The proliferation index of the PlexinA1 positive staining group (567.69±125.61) was significantly higher than that of the negative group (369.58±116.88) (P < 0.01).Therefore we can make some conclusions that Sema6D and its receptor PlexinA1 may play an important role in the occurrence and development of gastric carcinoma, and be related to tumor angiogenesis and proliferation. This is the first time to investigate the expression of Sema6D and its receptor PlexinA1 in gastric carcinoma and its clinical significance, which provide a new knowledge on the pathogenesis of gastric carcinoma, and may represent a new therapeutic target for gastric carcinoma treatment.

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CLC: > Medicine, health > Oncology > Gastrointestinal Cancer > Gastric neoplasms
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