知識

血管新生和癌症

血管新生和癌的生長及轉移

血管新生對惡性腫瘤(癌)的生長起著決定作用。一方面新血管保證了癌細胞的氧供、營養及代謝産物的排泄以促進其生長;另一方面癌細胞又借助新血管向身體其他部分轉移。腫瘤剛形成,大小不超過1~2㎣時,不需要新生血管,癌細胞只需直接吸收周遭環境的養份即可存活。超過1~2㎣的癌組織就必須靠新生血管來供應養份。對於這樣的惡性腫瘤,只要能夠抑制血管新生,切斷惡性腫瘤的營養供給來源,就可以讓腫瘤餓死。

血管內皮成長因子(VEGF) 由癌細胞等分泌產生,具有誘導血管新生的作用。VEGF通過與血管內皮細胞生長因子受體結合,刺激血管內皮細胞活化、增殖和遷移,促進新生血管形成。

控制新生血管對治療癌症的作用

上世紀70年代初期,哈佛大學的Judah Folkman博士就建議采用血管生成抑制劑控制新生血管的生長去治療各種癌症,剝奪癌細胞的氧氣和養分供應,同時使之産生的代謝産物堆積,近而控制癌細胞的生長和轉移。

主要過程如下

  1. 抑制血管生成促進因子的産生
  2. 抑制降解酶的産生
  3. 抑制血管壁細胞分裂增生
  4. 抑制血管壁細胞移動
  5. 抑制血管壁細胞活化
參考文獻
  1. Folkman J. Role of angiogenesis in tumor growth and metastasis. Semin Oncol, 2002 Dec 29 (6 Suppl 16), 15-8
  2. Daly ME; Makris A; Reed M; Lewis CE. Hemostatic regulators of tumor angiogenesis: a source of antiangiogenic agents for cancer treatment?. J Natl Cancer Inst 2003 Nov 19, 95(22), 1660-73.
  3. Heath VL; Bicknell R. Anticancer strategies involving the vasculature. Nat Rev Clin Oncol 2009 Jul 6(7), 395-404.
  4. Chung AS; Lee J; Ferrara N. Targeting the tumour vasculature: insights from physiological angiogenesis. Nat Rev Cancer 2010 Jul, 10(7), 505-514.
  5. Ellis LM, Hicklin DJ. VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer. 2008 Aug;8(8):579-591. doi: 10.1038/nrc2403.
  6. Zeng G, Taylor SM, McColm JR, Kappas NC, Kearney JB, Williams LH, Hartnett ME, Bautch VL. Orientation of endothelial cell division is regulated by VEGF signaling during blood vessel formation. Blood. 2007 Feb 15;109(4):1345-1352
  7. Hidalgo M, Eckhardt SG. Development of matrix metalloproteinase inhibitors in cancer therapy. J Natl Cancer Inst. 2001 Feb 7;93(3):178-193.
  8. Avraamides CJ, Garmy-Susini B, Varner JA. Integrins in angiogenesis and lymphangiogenesis. Nat Rev Cancer. 2008 Aug;8(8):604-617. doi: 10.1038/nrc2353.
  9. Cook KM, Figg WD. Angiogenesis inhibitors: current strategies and future prospects. CA Cancer J Clin. 2010 Jul-Aug;60(4):222-43. doi: 10.3322/caac.20075.
  10. In-sook Ahn; Steven Grekin; Stephen Verral; John Croft. An Ethanolic extract from a shark having potent anti-angiogenic activity: its anti-angiogenic mechanism and clinical application. Poster session: March 9, 2006 San Diego, California, U.S.A.
  11. Satoru Furukawa. Shark lipids for malignant diseases. December 12, 2005 Annual Meeting of Korean Society of Cancer Prevention.
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