CNTN-1、VEGF-C和VEGFR-3在胃癌組織中的表達及其臨床意義_《中國普外基礎與臨床雜志》

作者：

吳生華 ¹ , 俞繼衛 ¹ , 鄭林海 ¹ , 吳巨鋼 ¹ , 倪曉春 ¹ , 李曉強 ² , 杜光燁 ² , 姜波健 ¹

1.上海交通大學醫學院附屬第三人民醫院普外科(上海 201900);;
2.上海交通大學醫學院附屬第三人民醫院病理科(上海 201900);

關鍵詞：

胃癌接觸蛋白-1 血管內皮生長因子血管內皮生長因子受體 D2-40 淋巴結轉移

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目的探討神經細胞黏附分子——接觸蛋白-1(CNTN-1)、血管內皮生長因子-C(VEGF-C)及其受體VEGFR-3(Flt-4)在原發性胃癌組織中的表達，并分析三者的相關性及其與臨床病理特征的關系。方法選取68例原發性胃癌患者腫瘤原發灶和正常胃黏膜組織標本，行免疫組化染色檢測VEGF-C、VEGFR-3和CNTN-1蛋白表達，測定VEGFR-3陽性淋巴管密度(FVD)和D2-40陽性淋巴管密度(LVD)。結果胃癌組織中VEGF-C、VEGFR-3和CNTN-1蛋白表達陽性率分別為57.4%(39/68)、60.3%(41/68)和55.9%(38/68)，顯著高于正常胃黏膜組織〔20.6%(14/68)、23.5%(16/68)、16.2%(11/68)〕，P=0.000。在TNM分期較晚、發生淋巴管浸潤和淋巴結轉移的患者其腫瘤組織中三者的表達陽性率均較高(P lt;0.05)。CNTN-1蛋白表達與VEGF-C(r=0.372，P=0.002)及VEGFR-3蛋白(r=0.308，P=0.011)表達之間呈正相關。68例患者腫瘤組織中FVD為(10.41±9.38)個/HP，明顯低于其LVD〔(18.19±7.44)個/HP〕，P=0.000。在TNM分期較晚、有淋巴管浸潤和淋巴結轉移的患者腫瘤組織中，FVD與LVD均較高(P lt;0.05)。VEGF-C和CNTN-1蛋白表達陽性者FVD明顯高于表達陰性者(P=0.029和P=0.003); LVD與CNTN1(P=0.727)、VEGF-C(P=0.173)和VEGFR-3蛋白(P=0.924)表達均無關。 VEGF-C、VEGFR-3及CNTN-1蛋白表達陽性患者術后生存率分別較表達陰性患者低(P lt;0.05)。結論CNTN-1蛋白在胃癌組織中高表達，與VEGF-C和VEGFR-3蛋白表達相關，聯合檢測對判斷胃癌侵襲性和預后有重要參考價值。 VEGF-C可能通過CNTN-1通路介導淋巴管生成，從而促進胃癌的淋巴浸潤。

引用本文： 吳生華,俞繼衛,鄭林海,吳巨鋼,倪曉春,李曉強,杜光燁,姜波健. CNTN-1、VEGF-C和VEGFR-3在胃癌組織中的表達及其臨床意義. 中國普外基礎與臨床雜志, 2011, 18(2): 142-148. doi: 復制

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2.	Lohela M, Bry M, Tammela T, et al. VEGFs and receptors involved in angiogenesis versus lymphangiogenesis [J]. Curr Opin Cell Biol, 2009, 21(2): 154165.
3.	Matsumura S, Oue N, Mitani Y, et al. DNA demethylation of vascular endothelial growth factorC is associated with gene expression and its possible involvement of lymphangiogenesis in gastric cancer [J]. Int J Cancer, 2007, 120(8): 16891695.
4.	Mkinen T, Norrmén C, Petrova TV. Molecular mechanisms of lymphatic vascular development [J]. Cell Mol Life Sci, 2007, 64(15): 19151929.
5.	Morita H, Ishikawa Y, AkishimaFukasawa Y, et al. Histopathological predictor for regional lymph node metastasis in gastric cancer [J]. Virchows Arch, 2009, 454(2): 143151.
6.	Su JL, Yang PC, Shih JY, et al. The VEGFC/Flt4 axis promotes invasion and metastasis of cancer cells [J]. Cancer Cell, 2006, 9(3): 209223.
7.	Su JL, Yang CY, Shih JY, et al. Knockdown of contactin1 expression suppresses invasion and metastasis of lung adenocarcinoma [J]. Cancer Res, 2006, 66(5): 25532561.
8.	Yonemura Y, Endou Y, Tabachi K, et al. Evaluation of lymphatic invasion in primary gastric cancer by a new monoclonal antibody, D240 [J]. Hum Pathol, 2006, 37(9): 11931199.
9.	Kodama M, Kitadai Y, Tanaka M, et al. Vascular endothelial growth factor C stimulates progression of human gastric cancer via both autocrine and paracrine mechanisms [J]. Clin Cancer Res, 2008, 14(22): 72057214.
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12.	Skobe M, Dana R. Blocking the path of lymphatic vessels [J]. Nat Med, 2009, 15(9): 993994.
13.	Da MX, Wu XT, Wang J, et al. Expression of cyclooxygenase2 and vascular endothelial growth factorC correlates with lymphangiogenesis and lymphatic invasion in human gastric cancer [J]. Arch Med Res, 2008, 39(1): 9299.
14.	吳立剛, 劉奇倫, 胡志強. MMP2和VEGFC在甲狀腺乳頭狀癌中的表達及臨床意義 [J]. 中國普外基礎與臨床雜志, 2009, 16(11): 906910.
15.	黃桂林, 侯吉學, 吳毅平. 乳腺癌患者血清VEGFC水平與癌組織CerbB2蛋白的表達及臨床意義 [J]. 中國普外基礎與臨床雜志, 2009, 16(7): 514517.
16.	Wang XL, Fang JP, Tang RY, et al. Different significance between intratumoral and peritumoral lymphatic vessel density in gastric cancer: a retrospective study of 123 cases [J]. BMC Cancer, 2010, 10: 299.
17.	Vondenhoff MF, Greuter M, Goverse G, et al. LTbetaR signaling induces cytokine expression and upregulates lymphangiogenic factors in lymph node anlagen [J]. J Immunol, 2009, 182(9): 54395445.
18.	He M, Cheng Y, Li W, et al. Vascular endothelial growth factor C promotes cervical cancer metastasis via upregulation and activation of RhoA/ROCK2/moesin cascade [J]. BMC Cancer, 2010, 10: 170.
19.	Sung JY, Lee S, Kim YW, et al. Vascular endothelial growth factor receptor3 is a favorable prognostic factor in advanced gastric carcinoma [J]. Oncol Rep, 2008, 19(4): 939944.
20.	Revest J M, FaivreSarrailh C, Maeda N, et al. The interaction between F3 immunoglobulin domains and protein tyrosine phosphatases zeta/beta triggers bidirectional signalling between neurons and glial cells [J]. Eur J Neurosci, 1999, 11(4): 11341147.
21.	Sakurai T, Lustig M, Nativ M, et al. Induction of neurite outgrowth through contactin and NrCAM by extracellular regions of glial receptor tyrosine phosphatase beta [J]. J Cell Biol, 1997, 136(4): 907918.
22.	Zeng L, D’Alessandri L, Kalousek MB, et al. Protein tyrosine phosphatase alpha (PTPalpha) and contactin form a novel neuronal receptor complex linked to the intracellular tyrosine kinase fyn [J]. J Cell Biol, 1999, 147(4): 707714.
23.	Huang J, Asawa T, Takato T, et al. Cooperative roles of Fyn and cortactin in cell migration of metastatic murine melanoma [J]. J Biol Chem, 2003, 278(48): 4836748376.

1. Albuquerque RJ, Hayashi T, Cho WG, et al. Alternatively spliced vascular endothelial growth factor receptor2 is an essential endogenous inhibitor of lymphatic vessel growth [J]. Nat Med, 2009, 15(9): 10231030.
2. Lohela M, Bry M, Tammela T, et al. VEGFs and receptors involved in angiogenesis versus lymphangiogenesis [J]. Curr Opin Cell Biol, 2009, 21(2): 154165.
3. Matsumura S, Oue N, Mitani Y, et al. DNA demethylation of vascular endothelial growth factorC is associated with gene expression and its possible involvement of lymphangiogenesis in gastric cancer [J]. Int J Cancer, 2007, 120(8): 16891695.
4. Mkinen T, Norrmén C, Petrova TV. Molecular mechanisms of lymphatic vascular development [J]. Cell Mol Life Sci, 2007, 64(15): 19151929.
5. Morita H, Ishikawa Y, AkishimaFukasawa Y, et al. Histopathological predictor for regional lymph node metastasis in gastric cancer [J]. Virchows Arch, 2009, 454(2): 143151.
6. Su JL, Yang PC, Shih JY, et al. The VEGFC/Flt4 axis promotes invasion and metastasis of cancer cells [J]. Cancer Cell, 2006, 9(3): 209223.
7. Su JL, Yang CY, Shih JY, et al. Knockdown of contactin1 expression suppresses invasion and metastasis of lung adenocarcinoma [J]. Cancer Res, 2006, 66(5): 25532561.
8. Yonemura Y, Endou Y, Tabachi K, et al. Evaluation of lymphatic invasion in primary gastric cancer by a new monoclonal antibody, D240 [J]. Hum Pathol, 2006, 37(9): 11931199.
9. Kodama M, Kitadai Y, Tanaka M, et al. Vascular endothelial growth factor C stimulates progression of human gastric cancer via both autocrine and paracrine mechanisms [J]. Clin Cancer Res, 2008, 14(22): 72057214.
10. Sobin LH, Fleming ID. TNM Classification of Malignant Tumors, fifth edition (1997). Union Internationale Contre le Cancer and the American Joint Committee on Cancer [J]. Cancer, 1997, 80(9): 18031804.
11. Weidner N, Semple JP, Welch WR, et al. Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma [J]. N Engl J Med, 1991, 324(1): 18.
12. Skobe M, Dana R. Blocking the path of lymphatic vessels [J]. Nat Med, 2009, 15(9): 993994.
13. Da MX, Wu XT, Wang J, et al. Expression of cyclooxygenase2 and vascular endothelial growth factorC correlates with lymphangiogenesis and lymphatic invasion in human gastric cancer [J]. Arch Med Res, 2008, 39(1): 9299.
14. 吳立剛, 劉奇倫, 胡志強. MMP2和VEGFC在甲狀腺乳頭狀癌中的表達及臨床意義 [J]. 中國普外基礎與臨床雜志, 2009, 16(11): 906910.
15. 黃桂林, 侯吉學, 吳毅平. 乳腺癌患者血清VEGFC水平與癌組織CerbB2蛋白的表達及臨床意義 [J]. 中國普外基礎與臨床雜志, 2009, 16(7): 514517.
16. Wang XL, Fang JP, Tang RY, et al. Different significance between intratumoral and peritumoral lymphatic vessel density in gastric cancer: a retrospective study of 123 cases [J]. BMC Cancer, 2010, 10: 299.
17. Vondenhoff MF, Greuter M, Goverse G, et al. LTbetaR signaling induces cytokine expression and upregulates lymphangiogenic factors in lymph node anlagen [J]. J Immunol, 2009, 182(9): 54395445.
18. He M, Cheng Y, Li W, et al. Vascular endothelial growth factor C promotes cervical cancer metastasis via upregulation and activation of RhoA/ROCK2/moesin cascade [J]. BMC Cancer, 2010, 10: 170.
19. Sung JY, Lee S, Kim YW, et al. Vascular endothelial growth factor receptor3 is a favorable prognostic factor in advanced gastric carcinoma [J]. Oncol Rep, 2008, 19(4): 939944.
20. Revest J M, FaivreSarrailh C, Maeda N, et al. The interaction between F3 immunoglobulin domains and protein tyrosine phosphatases zeta/beta triggers bidirectional signalling between neurons and glial cells [J]. Eur J Neurosci, 1999, 11(4): 11341147.
21. Sakurai T, Lustig M, Nativ M, et al. Induction of neurite outgrowth through contactin and NrCAM by extracellular regions of glial receptor tyrosine phosphatase beta [J]. J Cell Biol, 1997, 136(4): 907918.
22. Zeng L, D’Alessandri L, Kalousek MB, et al. Protein tyrosine phosphatase alpha (PTPalpha) and contactin form a novel neuronal receptor complex linked to the intracellular tyrosine kinase fyn [J]. J Cell Biol, 1999, 147(4): 707714.
23. Huang J, Asawa T, Takato T, et al. Cooperative roles of Fyn and cortactin in cell migration of metastatic murine melanoma [J]. J Biol Chem, 2003, 278(48): 4836748376.

《中國普外基礎與臨床雜志》

CNTN-1、VEGF-C和VEGFR-3在胃癌組織中的表達及其臨床意義

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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《中國普外基礎與臨床雜志》

CNTN-1、VEGF-C和VEGFR-3在胃癌組織中的表達及其臨床意義

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

摘要全文圖表視頻參考文獻施引文獻補充材料