胰腺癌的浸润和转移研究进展
郑海涛,赵鸿鹏,卢俊, 山东大学山东省立医院普外科 山东省济南市 250012
通讯作者:卢俊,250012, 山东省济南市,山东大学山东省立医院普外科. lujunsd@126.com
电话: 0531-86620239
收稿日期:2005-01-21 接受日期:2005-04-01
摘要浸润和转移是恶性肿瘤重要的生物学特征，尤其转移是绝大多数恶性肿瘤的致死因素.此过程涉及到黏附分子、血管和淋巴管的形成、转移促进和抑制基因、细胞的运动和趋化性等.本文综述了这几方面近年来在胰腺癌中分子生物学方面的研究进展.
, 百拇医药
郑海涛,赵鸿鹏, 卢俊.胰腺癌的浸润和转移研究进展.世界华人消化杂志 2005;13(10):1219-1222
Li YJ, Meng YX, Ji XR. Relationship betweenexpressions of E-cadherin and alpha-catenin and biological behaviors
of human pancreatic cancer. HepatobiliaryPancreat Dis Int 2003;2:471-477
2 Sawai H, Funahashi H, Yamamoto M, Okada Y, Hayakawa T, Tanaka M,Takeyama H, Manabe T. Interleukin-1a
enhances integrin a6b1 expression andmetastatic capability of human pancreatic cancer. Oncology 2003;65:167-173
, 百拇医药
3 Takada M, Hirata K, Ajiki T, Suzuki Y, Kuroda Y. Expression ofreceptor for advanced glycation end products (RAGE)
and MMP-9 in human pancreatic cancer cells.Hepatogas-troenterology 2004;51:928-930
4 Kohlgraf KG, Gawron AJ, Higashi M, Meza JL, Burdick MD, Kitajima S,Kelly DL, Caffrey TC, Hollingsworth MA.
Contribution of the MUC1 tandem repeat andcytoplasmic tail to invasive and metastatic properties of apancreatic
, http://www.100md.com
cancer cell line. Cancer Res 2003;63:5011-5020
5 Hinoda Y, Ikematsu Y, Horinochi M, Sato S, Yamamoto K, Nakano T,Fukui M, Suehiro Y, Hamanaka Y, Nishikawa Y,Kida H, Waki S, Oka M, Imai K, Yonezawa S.Increased expression of MUC1 in advanced pancreatic cancer.
J Gastroenterol 2003;38:1162-1166
6 Jinfeng M, Kimura W, Hirai I, Sakurai F, Moriya T, Mizutani M.Expression of MUC5AC and MUC6 in invasive ductal
, 百拇医药
carcinoma of the pancreas and relationshipwith prognosis. Int J Gastrointest Cancer 2003;34:9-18
7 Uchima Y, Sawada T, Nishihara T, Umekawa T, Ohira M, Ishikawa T,Nishino H, Hirakawa K. Identification of a
trypsinogen activity stimulating factorproduced by pancreatic cancer cells: its role in tumor invasion andmetastasis.
Int J Mol Med 2003;12:871-878
8 Tan X, Egami H, Kamohara H, Ishikawa S, Kurizaki T, Yoshida N,Tamori Y, Takai E, Hirota M, Ogawa M. Involvement
, 百拇医药
of the mitogen-activated protein kinasekinase 2 in the induction of cell dissociation in pancreatic cancer.
Int J Oncol 2004;24:65-73
9 Tan X, Tamori Y, Egami H, Ishikawa S, Kurizaki T, Takai E, HirotaM, Ogawa M. Analysis of invasion-metastasis
mechanism in pancreatic cancer: involvementof tight junction transmembrane protein occludin and MEK/ERK signal
transduction pathway in cancer celldissociation. Oncol Rep 2004;11:993-998
, http://www.100md.com
10 Lim YJ, Lee JK, Jang WY, Song SY, Lee KT, Paik SW, Rhee JC.Prognostic significance of maspin in pancreatic
ductal adenocarcinoma. Korean JIntern Med 2004;19:15-18
11 Buchholz M, Biebl A, Neebetae A, Wagner M, Iwamura T, Leder G,Adler G, Gress TM. SERPINE2 (protease nexin I)
promotes extracellular matrixproduction and localinvasion of pancreatic tumors in vivo.
, http://www.100md.com
Cancer Res 2003;63:4945-4951
12 Tsutsumi S, Yanagawa T, Shimura T, Kuwano H, Raz A. Autocrinemotility factor signaling enhances pancreatic
cancer metastasis. Clin Cancer Res 2004;10:7775-7784
13 Nakajima S, Doi R, Toyoda E, Tsuji S, Wada M, Koizumi M, TulachanSS, Ito D, Kami K, Mori T, Kawaguchi Y,Fujimoto K, Hosotani R, Imamura M. N-cadherinexpression and epithelial-mesenchymal transition in pancreatic
, http://www.100md.com
carcinoma. Clin Cancer Res 2004;10:4125-4133
14 Yamada T, Sato K, Komachi M, Malchinkhuu E, Tobo M, Kimura T,Kuwabara A, Yanagita Y, Ikeya T, Tanahashi Y,Ogawa T, Ohwada S, Morishita Y, OhtaH, Im DS, Tamoto K, Tomura H, Okajima F. Lysophosphatidic acid(LPA)in
malignant ascites stimulates motilityof human pancreatic cancer cells through LPA1. J Biol Chem 2004;279:6595-6605
15 Iki K, Takeo T, Kubozoe T, Aoki S, Hayashi J, Tsunoda T. Detectionof serum MMPs in tumor-bearing hamsters.
, http://www.100md.com
J Hepatobiliary Pancreat Surg 2002;9:478-484
16 Nagakawa Y, Aoki T, Kasuya K, Tsuchida A, Koyanagi Y. Histologicfeatures of venous invasion, expression of vascular
endothelial growth factor and matrixmetalloproteinase-2 and matrix metalloproteinase-9, and the relation withliver
metastasis in pancreatic cancer. Pancreas 2002;24:169-178
17 Balaz P, Friess H, Kondo Y, Zhu Z, Zimmermann A, BühlerMW. Human macrophage metalloelastase worsens the
, 百拇医药
prognosis of pancreatic cancer. AnnSurg 2002;235:519-527
18 Sato N, Maehara N, Goggins M. Gene expression profiling of tumor-stromalinteractions between pancreatic cancer
cells and stromal fibroblasts. CancerRes 2004;64:6950-6956
19 Li Z, Sclabas GM, Peng B, Hess KR, Abbruzzese JL, Evans DB, ChiaoPJ. Overexpression of synuclein-g in pancreatic
adenocarcinoma. Cancer 2004;101:58-65
, http://www.100md.com
20 曾益新. 肿瘤学. 第2版. 北京:人民卫生出版社, 2003:254-255
21 Sunamura M, Duda DG, Ghattas MH, Lozonschi L, Motoi F, Yamauchi J,Matsuno S, Shibahara S, Abraham NG.
Heme oxygenase-1 accelerates tumorangiogenesis of human pancreatic cancer. Angiogenesis 2003;6:15-24
22 Bühler P,Reber HA, Lavey RS, Tomlinson J, Bühler MW, Friess H, Hines OJ. Tumor hypoxia correlates with
, 百拇医药 metastatic tumor growth of pancreatic cancer in an orthotopic murine model. J Surg Res 2004;120:295-303
23 Tobita K, Kijima H, Dowaki S, Oida Y, Kashiwagi H, Ishii M, Sugio Y, Sekka T, Ohtani Y, Tanaka M, Inokuchi S,Makuuchi H. Thrombospondin-1 expression as a prognostic predictor of pancreatic ductal carcinoma.
Int J Oncol 2002;21:1185-1195
24 Hiraoka K, Hida Y, Miyamoto M, Oshikiri T, Suzuoki M, Nakakubo Y, Shinohara T, Itoh T, Shichinohe T, Kondo S,Kasahara N, Katoh H. High expression of tumor-associated antigen RCAS1 in pancreatic ductal adenocarcinoma is
, 百拇医药
an unfavorable prognostic marker. Int J Cancer 2002;99:418-423
25 Sato N, Parker AR, Fukushima N, Miyagi Y, Iacobuzio-Donahue CA, Eshleman JR, Goggins M. Epigenetic inactivation
of TFPI-2 as a common mechanism associated with growth and invasion of pancreatic ductal adenocarcinoma.
Oncogene 2004;24:850-858
26 Veit C, Genze F, Menke A, Hoeffert S, Gress TM, Gierschik P, Giehl K. Activation of phosphatidylinositol 3-kinase and
, 百拇医药
extracellular signal-regulated kinase is required for glial cell line-derived neurotrophic factor-induced migration and
invasion of pancreatic carcinoma cells. Cancer Res 2004;64:5291-5300
27 Uchima Y, Sawada T, Nishihara T, Maeda K, Ohira M, Hirakawa K. Inhibition and mechanism of action of a protease
inhibitor in human pancreaticcancer cells. Pancreas 2004;29:123-131
, http://www.100md.com
28 Mori T, Doi R, Koizumi M, Toyoda E, Ito D, Kami K, Masui T, Fujimoto K, Tamamura H, Hiramatsu K, Fujii N,Imamura M. CXCR4 antagonist inhibits stromal cell-derived factor 1-induced migration and invasion of human
pancreatic cancer. Mol Cancer Ther 2004;3:29-37
29 Farrow B, Rychahou P, O'Connor KL, Evers BM. Butyrate inhibits pancreatic cancer invasion.
J Gastrointest Surg 2003;7:864-870
, 百拇医药
30 Kaneko K, Satoh K, Masamune A, Satoh A, Shimosegawa T. Expression of ROCK-1 in human pancreatic cancer:
its down-regulation by morpholino oligo antisense can reduce the migration of pancreatic cancer cells in vitro.
Pancreas 2002;24:251-257
31 Kaneko K, Satoh K, Masamune A, Satoh A, Shimosegawa T. Myosin light chain kinase inhibitors can block invasion
, 百拇医药 and adhesion of human pancreatic cancer cell lines. Pancreas 2002;24:34-41
32 Masui T, Hosotani R, Tsuji S, Miyamoto Y, Yasuda S, Ida J, Nakajima S, Kawaguchi M, Kobayashi H, Koizumi M,Toyoda E, Tulachan S, Arii S, Doi R, Imamura M. Expression of METH-1 and METH-2 in pancreatic cancer.
Clin Cancer Res 2001;7:3437-3443
33 Jimenez RE, Hartwig W, Antoniu BA, Compton CC, Warshaw AL, Fernandez-Del Castillo C. Effect of matrix
, 百拇医药
metalloproteinase inhibition on pancreatic cancer invasion and metastasis: an additive strategy for cancer control.
Ann Surg 2000;231:644-654
34 Matsushita A, Onda M, Uchida E, Maekawa R, Yoshioka T. Antitumor effect of a new selective matrix metalloproteinase
inhibitor, MMI-166, on experimental pancreatic cancer. Int J Cancer 2001;92:434-440
35 Tomioka D, Maehara N, Kuba K, Mizumoto K, Tanaka M, Matsumoto K, Nakamura T. Inhibition of growth, invasion,and metastasis of human pancreatic carcinoma cells by NK4 in an orthotopic mouse model. Cancer Res
, http://www.100md.com
2001;61:7518-7524
36 Maehara N, Nagai E, Mizumoto K, Sato N, Matsumoto K, Nakamura T, Narumi K, Nukiwa T, Tanaka M. Gene
transduction of NK4, HGF antagonist, inhibits in vitro invasion and in vivo growth of human pancreatic cancer.
Clin Exp Metastasis 2002;19:417-426
37 Wen Y, Yan DH, Wang B, Spohn B, Ding Y, Shao R, Zou Y, Xie K, Hung MC. p202, an interferon-inducible protein,mediates multiple antitumor activities in human pancreatic cancer xenograft models. Cancer Res 2001;61:7142-7147
编辑 张海宁, 百拇医药( 郑海涛,赵鸿鹏,卢 俊)
通讯作者:卢俊,250012, 山东省济南市,山东大学山东省立医院普外科. lujunsd@126.com
电话: 0531-86620239
收稿日期:2005-01-21 接受日期:2005-04-01
摘要浸润和转移是恶性肿瘤重要的生物学特征，尤其转移是绝大多数恶性肿瘤的致死因素.此过程涉及到黏附分子、血管和淋巴管的形成、转移促进和抑制基因、细胞的运动和趋化性等.本文综述了这几方面近年来在胰腺癌中分子生物学方面的研究进展.
, 百拇医药
郑海涛,赵鸿鹏, 卢俊.胰腺癌的浸润和转移研究进展.世界华人消化杂志 2005;13(10):1219-1222
Li YJ, Meng YX, Ji XR. Relationship betweenexpressions of E-cadherin and alpha-catenin and biological behaviors
of human pancreatic cancer. HepatobiliaryPancreat Dis Int 2003;2:471-477
2 Sawai H, Funahashi H, Yamamoto M, Okada Y, Hayakawa T, Tanaka M,Takeyama H, Manabe T. Interleukin-1a
enhances integrin a6b1 expression andmetastatic capability of human pancreatic cancer. Oncology 2003;65:167-173
, 百拇医药
3 Takada M, Hirata K, Ajiki T, Suzuki Y, Kuroda Y. Expression ofreceptor for advanced glycation end products (RAGE)
and MMP-9 in human pancreatic cancer cells.Hepatogas-troenterology 2004;51:928-930
4 Kohlgraf KG, Gawron AJ, Higashi M, Meza JL, Burdick MD, Kitajima S,Kelly DL, Caffrey TC, Hollingsworth MA.
Contribution of the MUC1 tandem repeat andcytoplasmic tail to invasive and metastatic properties of apancreatic
, http://www.100md.com
cancer cell line. Cancer Res 2003;63:5011-5020
5 Hinoda Y, Ikematsu Y, Horinochi M, Sato S, Yamamoto K, Nakano T,Fukui M, Suehiro Y, Hamanaka Y, Nishikawa Y,Kida H, Waki S, Oka M, Imai K, Yonezawa S.Increased expression of MUC1 in advanced pancreatic cancer.
J Gastroenterol 2003;38:1162-1166
6 Jinfeng M, Kimura W, Hirai I, Sakurai F, Moriya T, Mizutani M.Expression of MUC5AC and MUC6 in invasive ductal
, 百拇医药
carcinoma of the pancreas and relationshipwith prognosis. Int J Gastrointest Cancer 2003;34:9-18
7 Uchima Y, Sawada T, Nishihara T, Umekawa T, Ohira M, Ishikawa T,Nishino H, Hirakawa K. Identification of a
trypsinogen activity stimulating factorproduced by pancreatic cancer cells: its role in tumor invasion andmetastasis.
Int J Mol Med 2003;12:871-878
8 Tan X, Egami H, Kamohara H, Ishikawa S, Kurizaki T, Yoshida N,Tamori Y, Takai E, Hirota M, Ogawa M. Involvement
, 百拇医药
of the mitogen-activated protein kinasekinase 2 in the induction of cell dissociation in pancreatic cancer.
Int J Oncol 2004;24:65-73
9 Tan X, Tamori Y, Egami H, Ishikawa S, Kurizaki T, Takai E, HirotaM, Ogawa M. Analysis of invasion-metastasis
mechanism in pancreatic cancer: involvementof tight junction transmembrane protein occludin and MEK/ERK signal
transduction pathway in cancer celldissociation. Oncol Rep 2004;11:993-998
, http://www.100md.com
10 Lim YJ, Lee JK, Jang WY, Song SY, Lee KT, Paik SW, Rhee JC.Prognostic significance of maspin in pancreatic
ductal adenocarcinoma. Korean JIntern Med 2004;19:15-18
11 Buchholz M, Biebl A, Neebetae A, Wagner M, Iwamura T, Leder G,Adler G, Gress TM. SERPINE2 (protease nexin I)
promotes extracellular matrixproduction and localinvasion of pancreatic tumors in vivo.
, http://www.100md.com
Cancer Res 2003;63:4945-4951
12 Tsutsumi S, Yanagawa T, Shimura T, Kuwano H, Raz A. Autocrinemotility factor signaling enhances pancreatic
cancer metastasis. Clin Cancer Res 2004;10:7775-7784
13 Nakajima S, Doi R, Toyoda E, Tsuji S, Wada M, Koizumi M, TulachanSS, Ito D, Kami K, Mori T, Kawaguchi Y,Fujimoto K, Hosotani R, Imamura M. N-cadherinexpression and epithelial-mesenchymal transition in pancreatic
, http://www.100md.com
carcinoma. Clin Cancer Res 2004;10:4125-4133
14 Yamada T, Sato K, Komachi M, Malchinkhuu E, Tobo M, Kimura T,Kuwabara A, Yanagita Y, Ikeya T, Tanahashi Y,Ogawa T, Ohwada S, Morishita Y, OhtaH, Im DS, Tamoto K, Tomura H, Okajima F. Lysophosphatidic acid(LPA)in
malignant ascites stimulates motilityof human pancreatic cancer cells through LPA1. J Biol Chem 2004;279:6595-6605
15 Iki K, Takeo T, Kubozoe T, Aoki S, Hayashi J, Tsunoda T. Detectionof serum MMPs in tumor-bearing hamsters.
, http://www.100md.com
J Hepatobiliary Pancreat Surg 2002;9:478-484
16 Nagakawa Y, Aoki T, Kasuya K, Tsuchida A, Koyanagi Y. Histologicfeatures of venous invasion, expression of vascular
endothelial growth factor and matrixmetalloproteinase-2 and matrix metalloproteinase-9, and the relation withliver
metastasis in pancreatic cancer. Pancreas 2002;24:169-178
17 Balaz P, Friess H, Kondo Y, Zhu Z, Zimmermann A, BühlerMW. Human macrophage metalloelastase worsens the
, 百拇医药
prognosis of pancreatic cancer. AnnSurg 2002;235:519-527
18 Sato N, Maehara N, Goggins M. Gene expression profiling of tumor-stromalinteractions between pancreatic cancer
cells and stromal fibroblasts. CancerRes 2004;64:6950-6956
19 Li Z, Sclabas GM, Peng B, Hess KR, Abbruzzese JL, Evans DB, ChiaoPJ. Overexpression of synuclein-g in pancreatic
adenocarcinoma. Cancer 2004;101:58-65
, http://www.100md.com
20 曾益新. 肿瘤学. 第2版. 北京:人民卫生出版社, 2003:254-255
21 Sunamura M, Duda DG, Ghattas MH, Lozonschi L, Motoi F, Yamauchi J,Matsuno S, Shibahara S, Abraham NG.
Heme oxygenase-1 accelerates tumorangiogenesis of human pancreatic cancer. Angiogenesis 2003;6:15-24
22 Bühler P,Reber HA, Lavey RS, Tomlinson J, Bühler MW, Friess H, Hines OJ. Tumor hypoxia correlates with
, 百拇医药 metastatic tumor growth of pancreatic cancer in an orthotopic murine model. J Surg Res 2004;120:295-303
23 Tobita K, Kijima H, Dowaki S, Oida Y, Kashiwagi H, Ishii M, Sugio Y, Sekka T, Ohtani Y, Tanaka M, Inokuchi S,Makuuchi H. Thrombospondin-1 expression as a prognostic predictor of pancreatic ductal carcinoma.
Int J Oncol 2002;21:1185-1195
24 Hiraoka K, Hida Y, Miyamoto M, Oshikiri T, Suzuoki M, Nakakubo Y, Shinohara T, Itoh T, Shichinohe T, Kondo S,Kasahara N, Katoh H. High expression of tumor-associated antigen RCAS1 in pancreatic ductal adenocarcinoma is
, 百拇医药
an unfavorable prognostic marker. Int J Cancer 2002;99:418-423
25 Sato N, Parker AR, Fukushima N, Miyagi Y, Iacobuzio-Donahue CA, Eshleman JR, Goggins M. Epigenetic inactivation
of TFPI-2 as a common mechanism associated with growth and invasion of pancreatic ductal adenocarcinoma.
Oncogene 2004;24:850-858
26 Veit C, Genze F, Menke A, Hoeffert S, Gress TM, Gierschik P, Giehl K. Activation of phosphatidylinositol 3-kinase and
, 百拇医药
extracellular signal-regulated kinase is required for glial cell line-derived neurotrophic factor-induced migration and
invasion of pancreatic carcinoma cells. Cancer Res 2004;64:5291-5300
27 Uchima Y, Sawada T, Nishihara T, Maeda K, Ohira M, Hirakawa K. Inhibition and mechanism of action of a protease
inhibitor in human pancreaticcancer cells. Pancreas 2004;29:123-131
, http://www.100md.com
28 Mori T, Doi R, Koizumi M, Toyoda E, Ito D, Kami K, Masui T, Fujimoto K, Tamamura H, Hiramatsu K, Fujii N,Imamura M. CXCR4 antagonist inhibits stromal cell-derived factor 1-induced migration and invasion of human
pancreatic cancer. Mol Cancer Ther 2004;3:29-37
29 Farrow B, Rychahou P, O'Connor KL, Evers BM. Butyrate inhibits pancreatic cancer invasion.
J Gastrointest Surg 2003;7:864-870
, 百拇医药
30 Kaneko K, Satoh K, Masamune A, Satoh A, Shimosegawa T. Expression of ROCK-1 in human pancreatic cancer:
its down-regulation by morpholino oligo antisense can reduce the migration of pancreatic cancer cells in vitro.
Pancreas 2002;24:251-257
31 Kaneko K, Satoh K, Masamune A, Satoh A, Shimosegawa T. Myosin light chain kinase inhibitors can block invasion
, 百拇医药 and adhesion of human pancreatic cancer cell lines. Pancreas 2002;24:34-41
32 Masui T, Hosotani R, Tsuji S, Miyamoto Y, Yasuda S, Ida J, Nakajima S, Kawaguchi M, Kobayashi H, Koizumi M,Toyoda E, Tulachan S, Arii S, Doi R, Imamura M. Expression of METH-1 and METH-2 in pancreatic cancer.
Clin Cancer Res 2001;7:3437-3443
33 Jimenez RE, Hartwig W, Antoniu BA, Compton CC, Warshaw AL, Fernandez-Del Castillo C. Effect of matrix
, 百拇医药
metalloproteinase inhibition on pancreatic cancer invasion and metastasis: an additive strategy for cancer control.
Ann Surg 2000;231:644-654
34 Matsushita A, Onda M, Uchida E, Maekawa R, Yoshioka T. Antitumor effect of a new selective matrix metalloproteinase
inhibitor, MMI-166, on experimental pancreatic cancer. Int J Cancer 2001;92:434-440
35 Tomioka D, Maehara N, Kuba K, Mizumoto K, Tanaka M, Matsumoto K, Nakamura T. Inhibition of growth, invasion,and metastasis of human pancreatic carcinoma cells by NK4 in an orthotopic mouse model. Cancer Res
, http://www.100md.com
2001;61:7518-7524
36 Maehara N, Nagai E, Mizumoto K, Sato N, Matsumoto K, Nakamura T, Narumi K, Nukiwa T, Tanaka M. Gene
transduction of NK4, HGF antagonist, inhibits in vitro invasion and in vivo growth of human pancreatic cancer.
Clin Exp Metastasis 2002;19:417-426
37 Wen Y, Yan DH, Wang B, Spohn B, Ding Y, Shao R, Zou Y, Xie K, Hung MC. p202, an interferon-inducible protein,mediates multiple antitumor activities in human pancreatic cancer xenograft models. Cancer Res 2001;61:7142-7147
编辑 张海宁, 百拇医药( 郑海涛,赵鸿鹏,卢 俊)
