淋巴管生成因子與消化道腫瘤_《中國普外基礎與臨床雜志》

作者：

達明緒 , 伍曉汀 , 羅婷

四川大學華西醫院普外科（成都610041）;

關鍵詞：

血管內皮生長因子-C 血管內皮生長因子-D 淋巴管生成消化道腫瘤

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【摘要】目的介紹VEGFC和VEGFD在淋巴管生成及消化道腫瘤淋巴轉移中的作用的有關研究進展。
方法對近年來VEGFC和VEGFD的結構功能特點、及其在淋巴管生成和消化道腫瘤淋巴轉移中的作用的研究進展進行綜述和分析。
結果 VEGFC和VEGFD可促進血管、淋巴管生成和淋巴轉移。胃癌中VEGFC mRNA及其蛋白表達與淋巴侵犯、靜脈侵犯、淋巴結轉移及低的5年生存率相關； VEGFC在食管癌和結直腸癌中的作用以及VEGFD在結直腸癌中的作用有待進一步研究。
結論 VEGFC、VEGFD/VEGFR3信號通路可能成為控制腫瘤生長轉移的理想靶點，抗新生淋巴管治療有望成為腫瘤生物治療新模式。

引用本文： 達明緒,伍曉汀,羅婷. 淋巴管生成因子與消化道腫瘤. 中國普外基礎與臨床雜志, 2005, 12(6): 630-633. doi: 復制

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5.	Mandriota SJ, Jussila L, Jeltsch M, et al. Vascular endothelial growth factorCmediated lymphangiogenesis promotes tumour metastasis [J]. EMBO J, 2001; 20(4)672.
6.	Stacker SA, Caesar C, Baldwin ME, et al. VEGFD promotes the metastatic spread of tumor cells via the lymphatics [J]. Nat Med, 2001; 7(2)186.
7.	Veikkola T, Jussila L, Makinen T, et al. Signalling via vascular endothelial growth factor receptor3 is sufficient for lymphangiogenesis in transgenic mice [J]. EMBO J, 2001; 20(6)1223.
8.	Krishnan J, Kirkin V, Steffen A, et al. Differential in vivo and in vitro expression of vascular endothelial growth factor (VEGF)C and VEGFD in tumors and its relationship to lymphatic metastasis in immunocompetent rats [J]. Cancer Res, 2003; 63(3)713.
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13.	Ichikura T, Tomimatsu S, Ohkura E, et al. Prognostic significance of the expression of vascular endothelial growth factor (VEGF) and VEGFC in gastric carcinoma [J]. J Surg Oncol, 2001; 78(2)132.
14.	Takahashi A, Kono K, Itakura J, et al. Correlation of vascular endothelial growth factorC expression with tumorinfiltrating dendritic cells in gastric cancer [J]. Oncology, 2002; 62(2)121.
15.	Ishikawa M, Kitayama J, Kazama S, et al. Expression of vascular endothelial growth factor C and D (VEGFC and D) is an important risk factor for lymphatic metastasis in undifferentiated early gastric carcinoma [J]. Jpn J Clin Oncol, 2003; 33(1)21.
16.	Liu XE, Sun XD, Wu JM. Expression and significance of VEGFC and FLT4 in gastric cancer [J]. World J Gastroenterol, 2004; 10(3)352.
17.	Kitadai Y, Amioka T, Haruma K, et al. Clinicopathological significance of vascular endothelial growth factor (VEGF)C in human esophageal squamous cell carcinomas [J]. Int J Cancer, 2001; 93(5)662.
18.	Noguchi T, Takeno S, Shibata T, et al. VEGFC expression correlates with histological differentiation and metastasis in squamous cell carcinoma of the esophagus [J]. Oncol Rep, 2002; 9(5)995.
19.	Auvinen MI, Sihvo EI, Ruohtula T, et al. Incipient angiogenesis in Barrett’s epithelium and lymphangiogenesis in Barrett’s adenocarcinoma [J]. J Clin Oncol, 2002; 20(13)2971.
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22.	Andre T, Kotelevets L, Vaillant JC, et al. Vegf, VegfB, VegfC and their receptors KDR, FLT1 and FLT4 during the neoplastic progression of human colonic mucosa [J]. Int J Cancer, 2000; 86(2)174.
23.	White JD, Hewett PW, Kosuge D, et al. Vascular endothelial growth factorD expression is an independent prognostic marker for survival in colorectal carcinoma [J]. Cancer Res, 2002; 62(6)1669.
24.	Kawakami M, Furuhata T, Kimura Y, et al. Quantification of vascular endothelial growth factorC and its receptor3 messenger RNA with realtime quantitative polymerase chain reaction as a predictor of lymph node metastasis in human colorectal cancer [J]. Surgery, 2003; 133(3)300.
25.	Witte D, Thomas A, Ali N, et al. Expression of the vascular endothelial growth factor receptor3 (VEGFR3) and its ligand VEGFC in human colorectal adenocarcinoma [J]. Anticancer Res, 2002; 22(3)1463.

1. Joukov V, Pajusola K, Kaipainen A, et al. A novel vascular endothelial growth factor, VEGFC, is a ligand for the Flt4 (VEGFR3) and KDR (VEGFR2) receptor tyrosine kinases [J]. EMBO J, 1996; 15(7)1751.
2. Achen MG, Jeltsch M, Kukk E, et al. Vascular endothelial growth factor D (VEGFD) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4) [J]. Proc Natl Acad Sci USA, 1998; 95(2)548.
3. McColl BK, Baldwin ME, Roufail S, et al. Plasmin activates the lymphangiogenic growth factors VEGFC and VEGFD [J]. J Exp Med, 2003; 198(6)86.
4. Skobe M, Hawighorst T, Jackson DG, et al. Induction of tumor lymphangiogenesis by VEGFC promotes breast cancer metastasis [J]. Nat Med, 2001; 7(2)192.
5. Mandriota SJ, Jussila L, Jeltsch M, et al. Vascular endothelial growth factorCmediated lymphangiogenesis promotes tumour metastasis [J]. EMBO J, 2001; 20(4)672.
6. Stacker SA, Caesar C, Baldwin ME, et al. VEGFD promotes the metastatic spread of tumor cells via the lymphatics [J]. Nat Med, 2001; 7(2)186.
7. Veikkola T, Jussila L, Makinen T, et al. Signalling via vascular endothelial growth factor receptor3 is sufficient for lymphangiogenesis in transgenic mice [J]. EMBO J, 2001; 20(6)1223.
8. Krishnan J, Kirkin V, Steffen A, et al. Differential in vivo and in vitro expression of vascular endothelial growth factor (VEGF)C and VEGFD in tumors and its relationship to lymphatic metastasis in immunocompetent rats [J]. Cancer Res, 2003; 63(3)713.
9. Leu AJ, Berk DA, Lymboussaki A, et al. Absence of functional lymphatics within a murine sarcoma: a molecular and functional evaluation [J]. Cancer Res, 2000; 60(16)4324.
10. Padera TP, Kadambi A, di Tomaso E, et al. Lymphatic metastasis in the absence of functional intratumor lymphatics [J]. Science, 2002; 296(5574)1883.
11. Yonemura Y, Endo Y, Fujita H, et al. Role of vascular endothelial growth factor C expression in the development of lymph node metastasis in gastric cancer [J]. Clin Cancer Res, 1999; 5(7)1823.
12. Yonemura Y, Fushida S, Bando E, et al. Lymphangiogenesis and the vascular endothelial growth factor receptor (VEGFR)3 in gastric cancer [J]. Eur J Cancer, 2001; 37(7)918.
13. Ichikura T, Tomimatsu S, Ohkura E, et al. Prognostic significance of the expression of vascular endothelial growth factor (VEGF) and VEGFC in gastric carcinoma [J]. J Surg Oncol, 2001; 78(2)132.
14. Takahashi A, Kono K, Itakura J, et al. Correlation of vascular endothelial growth factorC expression with tumorinfiltrating dendritic cells in gastric cancer [J]. Oncology, 2002; 62(2)121.
15. Ishikawa M, Kitayama J, Kazama S, et al. Expression of vascular endothelial growth factor C and D (VEGFC and D) is an important risk factor for lymphatic metastasis in undifferentiated early gastric carcinoma [J]. Jpn J Clin Oncol, 2003; 33(1)21.
16. Liu XE, Sun XD, Wu JM. Expression and significance of VEGFC and FLT4 in gastric cancer [J]. World J Gastroenterol, 2004; 10(3)352.
17. Kitadai Y, Amioka T, Haruma K, et al. Clinicopathological significance of vascular endothelial growth factor (VEGF)C in human esophageal squamous cell carcinomas [J]. Int J Cancer, 2001; 93(5)662.
18. Noguchi T, Takeno S, Shibata T, et al. VEGFC expression correlates with histological differentiation and metastasis in squamous cell carcinoma of the esophagus [J]. Oncol Rep, 2002; 9(5)995.
19. Auvinen MI, Sihvo EI, Ruohtula T, et al. Incipient angiogenesis in Barrett’s epithelium and lymphangiogenesis in Barrett’s adenocarcinoma [J]. J Clin Oncol, 2002; 20(13)2971.
20. Furudoi A, Tanaka S, Haruma K, et al. Clinical significance of vascular endothelial growth factor C expression and angiogenesis at the deepest invasive site of advanced colorectal carcinoma [J]. Oncology, 2002; 62(2)157.
21. George ML, Tutton MG, Janssen F, et al. VEGFA, VEGFC, and VEGFD in colorectal cancer progression [J]. Neoplasia, 2001; 3(5)420.
22. Andre T, Kotelevets L, Vaillant JC, et al. Vegf, VegfB, VegfC and their receptors KDR, FLT1 and FLT4 during the neoplastic progression of human colonic mucosa [J]. Int J Cancer, 2000; 86(2)174.
23. White JD, Hewett PW, Kosuge D, et al. Vascular endothelial growth factorD expression is an independent prognostic marker for survival in colorectal carcinoma [J]. Cancer Res, 2002; 62(6)1669.
24. Kawakami M, Furuhata T, Kimura Y, et al. Quantification of vascular endothelial growth factorC and its receptor3 messenger RNA with realtime quantitative polymerase chain reaction as a predictor of lymph node metastasis in human colorectal cancer [J]. Surgery, 2003; 133(3)300.
25. Witte D, Thomas A, Ali N, et al. Expression of the vascular endothelial growth factor receptor3 (VEGFR3) and its ligand VEGFC in human colorectal adenocarcinoma [J]. Anticancer Res, 2002; 22(3)1463.

《中國普外基礎與臨床雜志》

淋巴管生成因子與消化道腫瘤

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《中國普外基礎與臨床雜志》

淋巴管生成因子與消化道腫瘤

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

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