胰腺癌細胞的嗜神經性與神經周浸潤機理的研究進展△_《中國普外基礎與臨床雜志》

作者：

張勇 , 閆宇 ,  黨誠學

西安交通大學醫學院第一附屬醫院腫瘤外科（陜西西安 710061）;

關鍵詞：

胰腺癌神經周浸潤嗜神經性神經生長因子腫瘤神經微環境

視頻：

導出 下載 收藏 掃碼 引用

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

目的綜述胰腺癌細胞神經周浸潤（perineural invasion, PNI）的發生機理，為胰腺癌治療尋找新的靶點。方法對包含有關胰腺癌PNI、嗜神經浸潤、神經-腫瘤微環境和神經生長因子的文獻進行分析，總結有關PNI的發生機理。結果胰腺組織本身具有的豐富神經支配和神經纖維鞘具有裂隙樣的結構是PNI的解剖基礎。癌細胞表達神經源性標志物或獲得嗜神經浸潤表型可能是PNI的病理基礎。腫瘤-神經微環境或神經生長因子家族及其相應受體可能是PNI的分子基礎。對于PNI，不僅僅在于癌細胞本身具有的嗜神經浸潤能力，也可能是癌細胞和神經纖維之間相互作用的結果。結論PNI的機理較復雜，尚沒有明確的定論，但相關機理將可能為胰腺癌的治療提供新的靶點。

引用本文： 張勇,閆宇,黨誠學. 胰腺癌細胞的嗜神經性與神經周浸潤機理的研究進展△. 中國普外基礎與臨床雜志, 2011, 18(1): 21-25. doi: 復制

1.	Kleeff J, Michalski C, Friess H, et al. Pancreatic cancer: from bench to 5year survival [J]. Pancreas, 2006, 33(2): 111118.
2.	Van den Broeck A, Sergeant G, Ectors N, et al. Patterns of recurrence after curative resection of pancreatic ductal adenocarcinoma [J]. Eur J Surg Oncol, 2009, 35(6): 600604.
3.	Keleg S, Büchler P, Ludwig R, et al. Invasion and metastasis in pancreatic cancer [J]. Mol Cancer, 2003, 2: 14.
4.	Akert K, Sandri C, Weibel ER, et al. The fine structure of the perineural endothelium [J]. Cell Tissue Res, 1976, 165(3): 281295.
5.	Batsakis JG. Nerves and neurotropic carcinomas [J]. Ann Otol Rhinol Laryngol, 1985, 94(4 Pt 1): 426427.
6.	Okamoto M, Nakamura Y, Imaizumi M. Peripheral nerve structure [J]. Saishin Igaku, 1968, 23(11): 22402252.
7.	黨誠學, 王健生, 任予, 等. 胰腺癌神經浸潤途徑的探討和臨床意義的研究 [J]. 中華肝膽外科雜志, 2001, 7(6): 357358.
8.	Rodin AE, Larson DL, Roberts DK. Nature of the perineural space invaded by prostatic carcinoma [J]. Cancer, 1967, 20(10): 17721779.
9.	Ballantyne AJ, Mccarten AB, Ibanez ML. The extension of cancer of the head and neck through peripheral nerves [J]. Am J Surg， 1963, 106: 651667.
10.	Kayahara M, Nakagawara H, Kitagawa H, et al. The nature of neural invasion by pancreatic cancer [J]. Pancreas, 2007, 35(3): 218223.
11.	Beger HG, Rau B, Gansauge F, et al. Treatment of pancreatic cancer: challenge of the facts [J]. World J Surg, 2003, 27(10): 10751084.
12.	Dang C, Zhang Y, Ma Q, et al. Expression of nerve growth factor receptors is correlated with progression and prognosis of human pancreatic cancer [J]. J Gastroenterol Hepatol, 2006, 21(5): 850858.
13.	Zhu Z, Friess H, diMola FF, et al. Nerve growth factor expression correlates with perineural invasion and pain in human pancreatic cancer [J]. J Clin Oncol, 1999, 17(8): 24192428.
14.	di Mola FF, di Sebastiano P. Pain and pain generation in pancreatic cancer [J]. Langenbecks Arch Surg, 2008, 393(6): 919922.
15.	Pour PM, Bell RH, Batra SK. Neural invasion in the staging of pancreatic cancer [J]. Pancreas, 2003, 26(4): 322325.
16.	Ozaki H, Hiraoka T, Mizumoto R, et al. The prognostic significance of lymph node metastasis and intrapancreatic perineural invasion in pancreatic cancer after curative resection [J]. Surg Today, 1999, 29(1): 1622.
17.	Cruveilhier J, Maladies des nerfs. Anatomic Pathologique du Corps Humain [M]. 2nd ed. Paris: J.B. Baillière, 1835: 3335.
18.	Ernst P. Uber das Wachstum und die Verbeitung bosartiger Geshwulstte, insbesondere des Krebes in den Lymphbahnen der Nerven [J]. Beitr Path Anat, 1905, 7(Suppl): 2951.
19.	Kuwayti K, Baggenstoss AH, Stauffer MH, et al. Carcinoma of the major intrahepatic and the extrahepatic bile ducts exclusive of the papilla of Vater [J]. Surg Gynecol Obstet, 1957, 104(3): 357366.
20.	Dunn M, Morgan MB, Beer TW. Perineural invasion: identification, significance, and a standardized definition [J]. Dermatol Surg, 2009, 35(2): 214221.
21.	Liebig C, Ayala G, Wilks JA, et al. Perineural invasion in cancer: a review of the literature [J]. Cancer, 2009, 115(15): 33793391.
22.	Znker KS, Entschladen F (eds): Neuronal activity in tumor tissue [A]. In: Progression in Experimental Tumor Research [M]. Basel: Karger, 2007: 132133.
23.	Eibl G, Reber HA. A xenograft nude mouse model for perineural invasion and recurrence in pancreatic cancer [J]. Pancreas, 2005, 31(3): 258262.
24.	Carlson JA, Dickersin GR, Sober AJ, et al. Desmoplastic neurotropic melanoma. A clinicopathologic analysis of 28 cases [J]. Cancer, 1995, 75(2): 478494.
25.	Watanabe H, Mizutani T, Haraguchi T, et al. SWI/SNF complex is essential for NRSFmediated suppression of neuronal genes in human nonsmall cell lung carcinoma cell lines [J]. Oncogene, 2006, 25(3): 470479.
26.	Chédotal A, Kerjan G, MoreauFauvarque C. The brain within the tumor: new roles for axon guidance molecules in cancers [J]. Cell Death Differ, 2005, 12(8): 10441056.
27.	Zhu Z, Kleeff J, Kayed H, et al. Nerve growth factor and enhancement of proliferation, invasion, and tumorigenicity of pancreatic carcinomas cells [J]. Mol Carcinog, 2002, 35(3): 138147.
28.	Zhang Y, Dang C, Ma Q, et al. Expression of nerve growth factor receptors and their prognostic value in human pancreatic cancer [J]. Oncol Rep, 2005, 14(1): 161171.
29.	Bockman DE, Büchler M, Beger HG. Interaction of pancreatic ductal carcinoma with nerves leads to nerve damage [J]. Gastroenterology, 1994, 107(1): 219230.
30.	鄭善川, 梁麗, 張玉茹, 等. GDNF及其受體Ret在腺樣囊性癌嗜神經侵襲和細胞增殖中作用的初步研究 [J]. 口腔醫學研究, 2010, 26(3): 380383.
31.	Ceyhan GO, Giese NA, Erkan M, et al. The neurotrophic factor artemin promotes pancreatic cancer invasion [J]. Ann Surg, 2006, 244(2): 274281.
32.	朱棟良, 羅地來, 羅剛, 等. Artemin、GFRα3在胰腺癌中的表達及其與胰腺癌神經浸潤轉移的相關性 [J]. 南方醫科大學學報, 2009, 29(3): 428431.
33.	Ben QW, Wang JC, Liu J, et al. Positive expression of L1CAM is associated with perineural invasion and poor outcome in pancreatic ductal adenocarcinoma [J]. Ann Surg Oncol, 2010, 17(8): 22132221.
34.	Farrow B, Albo D, Berger DH. The role of the tumor microenvironment in the progression of pancreatic cancer [J]. J Surg Res, 2008, 149(2): 319328.
35.	Ma J, Jiang Y, Jiang Y, et al. Expression of nerve growth factor and tyrosine kinase receptor A and correlation with perineural invasion in pancreatic cancer [J]. J Gastroenterol Hepatol, 2008, 23(12): 18521859.
36.	Okada Y, Eibl G, Duffy JP, et al. Glial cellderived neurotrophic factor upregulates the expression and activation of matrix metalloproteinase9 in human pancreatic cancer [J]. Surgery, 2003, 134(2): 293299.
37.	Iwahashi N, Nagasaka T, Tezel G, et al. Expression of glial cell linederived neurotrophic factor correlates with perineural invasion of bile duct carcinoma [J]. Cancer, 2002, 94(1): 167174.
38.	Podratz JL, Rodriguez E, Windebank AJ. Role of the extracellular matrix in myelination of peripheral nerve [J]. Glia, 2001, 35(1): 3540.
39.	Hill RE, Williams RE. A quantitative analysis of perineurial cell basement membrane collagen Ⅳ, laminin and fibronectin in diabetic and nondiabetic human sural nerve [J]. J Anat, 2002, 201(2): 185192.
40.	Vega JA, Esteban I, Naves FJ, et al. Immunohistochemical localization of laminin and type Ⅳ collagen in human cutaneous sensory nerve formations [J]. Anat Embryol (Berl), 1995, 191(1): 3339.
41.	Ryschich E, Khamidjanov A, Kerkadze V, et al. Promotion of tumor cell migration by extracellular matrix proteins in human pancreatic cancer [J]. Pancreas, 2009, 38(7): 804810.
42.	Wang W, Zhao H, Zhang S, et al. Patterns of expression and function of the p75NGFR protein in pancreatic cancer cells and tumours [J]. Eur J Surg Oncol, 2009, 35(8): 826832.
43.	Yao J, Ma Q, Wang L, et al. Pleiotrophin expression in human pancreatic cancer and its correlation with clinicopathological features, perineural invasion, and prognosis [J]. Dig Dis Sci, 2009, 54(4): 895901.
44.	Abiatari I, DeOliveira T, Kerkadze V, et al. Consensus transcriptome signature of perineural invasion in pancreatic carcinoma [J]. Mol Cancer Ther, 2009, 8(6): 14941504.

1. Kleeff J, Michalski C, Friess H, et al. Pancreatic cancer: from bench to 5year survival [J]. Pancreas, 2006, 33(2): 111118.
2. Van den Broeck A, Sergeant G, Ectors N, et al. Patterns of recurrence after curative resection of pancreatic ductal adenocarcinoma [J]. Eur J Surg Oncol, 2009, 35(6): 600604.
3. Keleg S, Büchler P, Ludwig R, et al. Invasion and metastasis in pancreatic cancer [J]. Mol Cancer, 2003, 2: 14.
4. Akert K, Sandri C, Weibel ER, et al. The fine structure of the perineural endothelium [J]. Cell Tissue Res, 1976, 165(3): 281295.
5. Batsakis JG. Nerves and neurotropic carcinomas [J]. Ann Otol Rhinol Laryngol, 1985, 94(4 Pt 1): 426427.
6. Okamoto M, Nakamura Y, Imaizumi M. Peripheral nerve structure [J]. Saishin Igaku, 1968, 23(11): 22402252.
7. 黨誠學, 王健生, 任予, 等. 胰腺癌神經浸潤途徑的探討和臨床意義的研究 [J]. 中華肝膽外科雜志, 2001, 7(6): 357358.
8. Rodin AE, Larson DL, Roberts DK. Nature of the perineural space invaded by prostatic carcinoma [J]. Cancer, 1967, 20(10): 17721779.
9. Ballantyne AJ, Mccarten AB, Ibanez ML. The extension of cancer of the head and neck through peripheral nerves [J]. Am J Surg， 1963, 106: 651667.
10. Kayahara M, Nakagawara H, Kitagawa H, et al. The nature of neural invasion by pancreatic cancer [J]. Pancreas, 2007, 35(3): 218223.
11. Beger HG, Rau B, Gansauge F, et al. Treatment of pancreatic cancer: challenge of the facts [J]. World J Surg, 2003, 27(10): 10751084.
12. Dang C, Zhang Y, Ma Q, et al. Expression of nerve growth factor receptors is correlated with progression and prognosis of human pancreatic cancer [J]. J Gastroenterol Hepatol, 2006, 21(5): 850858.
13. Zhu Z, Friess H, diMola FF, et al. Nerve growth factor expression correlates with perineural invasion and pain in human pancreatic cancer [J]. J Clin Oncol, 1999, 17(8): 24192428.
14. di Mola FF, di Sebastiano P. Pain and pain generation in pancreatic cancer [J]. Langenbecks Arch Surg, 2008, 393(6): 919922.
15. Pour PM, Bell RH, Batra SK. Neural invasion in the staging of pancreatic cancer [J]. Pancreas, 2003, 26(4): 322325.
16. Ozaki H, Hiraoka T, Mizumoto R, et al. The prognostic significance of lymph node metastasis and intrapancreatic perineural invasion in pancreatic cancer after curative resection [J]. Surg Today, 1999, 29(1): 1622.
17. Cruveilhier J, Maladies des nerfs. Anatomic Pathologique du Corps Humain [M]. 2nd ed. Paris: J.B. Baillière, 1835: 3335.
18. Ernst P. Uber das Wachstum und die Verbeitung bosartiger Geshwulstte, insbesondere des Krebes in den Lymphbahnen der Nerven [J]. Beitr Path Anat, 1905, 7(Suppl): 2951.
19. Kuwayti K, Baggenstoss AH, Stauffer MH, et al. Carcinoma of the major intrahepatic and the extrahepatic bile ducts exclusive of the papilla of Vater [J]. Surg Gynecol Obstet, 1957, 104(3): 357366.
20. Dunn M, Morgan MB, Beer TW. Perineural invasion: identification, significance, and a standardized definition [J]. Dermatol Surg, 2009, 35(2): 214221.
21. Liebig C, Ayala G, Wilks JA, et al. Perineural invasion in cancer: a review of the literature [J]. Cancer, 2009, 115(15): 33793391.
22. Znker KS, Entschladen F (eds): Neuronal activity in tumor tissue [A]. In: Progression in Experimental Tumor Research [M]. Basel: Karger, 2007: 132133.
23. Eibl G, Reber HA. A xenograft nude mouse model for perineural invasion and recurrence in pancreatic cancer [J]. Pancreas, 2005, 31(3): 258262.
24. Carlson JA, Dickersin GR, Sober AJ, et al. Desmoplastic neurotropic melanoma. A clinicopathologic analysis of 28 cases [J]. Cancer, 1995, 75(2): 478494.
25. Watanabe H, Mizutani T, Haraguchi T, et al. SWI/SNF complex is essential for NRSFmediated suppression of neuronal genes in human nonsmall cell lung carcinoma cell lines [J]. Oncogene, 2006, 25(3): 470479.
26. Chédotal A, Kerjan G, MoreauFauvarque C. The brain within the tumor: new roles for axon guidance molecules in cancers [J]. Cell Death Differ, 2005, 12(8): 10441056.
27. Zhu Z, Kleeff J, Kayed H, et al. Nerve growth factor and enhancement of proliferation, invasion, and tumorigenicity of pancreatic carcinomas cells [J]. Mol Carcinog, 2002, 35(3): 138147.
28. Zhang Y, Dang C, Ma Q, et al. Expression of nerve growth factor receptors and their prognostic value in human pancreatic cancer [J]. Oncol Rep, 2005, 14(1): 161171.
29. Bockman DE, Büchler M, Beger HG. Interaction of pancreatic ductal carcinoma with nerves leads to nerve damage [J]. Gastroenterology, 1994, 107(1): 219230.
30. 鄭善川, 梁麗, 張玉茹, 等. GDNF及其受體Ret在腺樣囊性癌嗜神經侵襲和細胞增殖中作用的初步研究 [J]. 口腔醫學研究, 2010, 26(3): 380383.
31. Ceyhan GO, Giese NA, Erkan M, et al. The neurotrophic factor artemin promotes pancreatic cancer invasion [J]. Ann Surg, 2006, 244(2): 274281.
32. 朱棟良, 羅地來, 羅剛, 等. Artemin、GFRα3在胰腺癌中的表達及其與胰腺癌神經浸潤轉移的相關性 [J]. 南方醫科大學學報, 2009, 29(3): 428431.
33. Ben QW, Wang JC, Liu J, et al. Positive expression of L1CAM is associated with perineural invasion and poor outcome in pancreatic ductal adenocarcinoma [J]. Ann Surg Oncol, 2010, 17(8): 22132221.
34. Farrow B, Albo D, Berger DH. The role of the tumor microenvironment in the progression of pancreatic cancer [J]. J Surg Res, 2008, 149(2): 319328.
35. Ma J, Jiang Y, Jiang Y, et al. Expression of nerve growth factor and tyrosine kinase receptor A and correlation with perineural invasion in pancreatic cancer [J]. J Gastroenterol Hepatol, 2008, 23(12): 18521859.
36. Okada Y, Eibl G, Duffy JP, et al. Glial cellderived neurotrophic factor upregulates the expression and activation of matrix metalloproteinase9 in human pancreatic cancer [J]. Surgery, 2003, 134(2): 293299.
37. Iwahashi N, Nagasaka T, Tezel G, et al. Expression of glial cell linederived neurotrophic factor correlates with perineural invasion of bile duct carcinoma [J]. Cancer, 2002, 94(1): 167174.
38. Podratz JL, Rodriguez E, Windebank AJ. Role of the extracellular matrix in myelination of peripheral nerve [J]. Glia, 2001, 35(1): 3540.
39. Hill RE, Williams RE. A quantitative analysis of perineurial cell basement membrane collagen Ⅳ, laminin and fibronectin in diabetic and nondiabetic human sural nerve [J]. J Anat, 2002, 201(2): 185192.
40. Vega JA, Esteban I, Naves FJ, et al. Immunohistochemical localization of laminin and type Ⅳ collagen in human cutaneous sensory nerve formations [J]. Anat Embryol (Berl), 1995, 191(1): 3339.
41. Ryschich E, Khamidjanov A, Kerkadze V, et al. Promotion of tumor cell migration by extracellular matrix proteins in human pancreatic cancer [J]. Pancreas, 2009, 38(7): 804810.
42. Wang W, Zhao H, Zhang S, et al. Patterns of expression and function of the p75NGFR protein in pancreatic cancer cells and tumours [J]. Eur J Surg Oncol, 2009, 35(8): 826832.
43. Yao J, Ma Q, Wang L, et al. Pleiotrophin expression in human pancreatic cancer and its correlation with clinicopathological features, perineural invasion, and prognosis [J]. Dig Dis Sci, 2009, 54(4): 895901.
44. Abiatari I, DeOliveira T, Kerkadze V, et al. Consensus transcriptome signature of perineural invasion in pancreatic carcinoma [J]. Mol Cancer Ther, 2009, 8(6): 14941504.

上一篇
重癥肌無力危象長期持續狀態成功脫離呼吸機一例

《中國普外基礎與臨床雜志》

胰腺癌細胞的嗜神經性與神經周浸潤機理的研究進展△

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

上一篇

Format

Content

《中國普外基礎與臨床雜志》

胰腺癌細胞的嗜神經性與神經周浸潤機理的研究進展△

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

上一篇

Format

Content

摘要全文圖表視頻參考文獻施引文獻補充材料