• 上海交通大學(xué)醫(yī)學(xué)院附屬第三人民醫(yī)院普外科（上海 201900）;

目的 介紹腫瘤干細(xì)胞在胃腸道腫瘤發(fā)生和轉(zhuǎn)移中的研究進(jìn)展。
方法 收集國(guó)內(nèi)、外近年來有關(guān)腫瘤干細(xì)胞與胃腸道腫瘤發(fā)生與轉(zhuǎn)移的研究進(jìn)展的文獻(xiàn)并作綜述。
結(jié)果 近年來的研究已發(fā)現(xiàn)在腫瘤細(xì)胞中存在著少量的具有干細(xì)胞樣特性的腫瘤細(xì)胞。這些腫瘤干細(xì)胞利用機(jī)體的干細(xì)胞-巢系統(tǒng)而在腫瘤的發(fā)生、維持生長(zhǎng)、增殖、轉(zhuǎn)移和復(fù)發(fā)中起著重要作用。此外，在耐受抗腫瘤藥物而導(dǎo)致的復(fù)發(fā)中發(fā)揮重要作用。在胃腸道腫瘤中，特別是在結(jié)直腸癌中，這些腫瘤起始細(xì)胞通常具有CD133+的特征。CD133+結(jié)腸癌細(xì)胞具有克隆形成能力、增殖能力、分化能力以及轉(zhuǎn)移瘤形成能力。同時(shí)，在骨轉(zhuǎn)移患者的外周血中也已發(fā)現(xiàn)有高含量的CD133 mRNA存在。
結(jié)論 CD133+腫瘤細(xì)胞的分子生物學(xué)特性以及腫瘤干細(xì)胞-巢系統(tǒng)的機(jī)理是開發(fā)更有效的腫瘤診治方法的基礎(chǔ)，并為靶向治療等新途徑提供理論依據(jù)。

引用本文： 張鵬,俞繼衛(wèi),姜波健. 腫瘤干細(xì)胞與胃腸道癌發(fā)生和轉(zhuǎn)移. 中國(guó)普外基礎(chǔ)與臨床雜志, 2009, 16(1): 81-84. doi: 復(fù)制

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13. 張建軍, 劉志明. MMP-9及TIMP-1在甲狀腺癌組織及外周血中的表達(dá)及臨床意義 [J] . 中國(guó)普外基礎(chǔ)與臨床雜志, 2007; 14(4)： 437.
14. 朱軍華， 陶凱雄， 王國(guó)斌. TNF-α對(duì)肝癌細(xì)胞VEGF和MMP-9表達(dá)的影響 [J] . 中國(guó)普外基礎(chǔ)與臨床雜志, 2005; 12(4)：384.
15. Müller A, Homey B, Soto H, et al . Involvement of chemokine receptors in breast cancer metastasis [J] . Nature, 2001; 410 (6824)： 50.
16. Wai PY, Kuo PC. The role of Osteopontin in tumor metastasis [J] . J Surg Res, 2004; 121(2)：228.
17. Balic M, Lin H, Young L, et al . Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype [J] . Clin Cancer Res, 2006; 12(19)： 5615.
18. Hugo H, Ackland ML, Blick T, et al . Epithelial-mesenchymal and mesenchymal-epithelial transitions in carcinoma progression [J] . J Cell Physiol, 2007; 213(2)： 374.
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20. Coussens LM, Tinkle CL, Hanahan D, et al . MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis [J] . Cell, 2000; 103(3)： 481.
21. Lyden D, Hattori K, Dias S, et al . Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth [J] . Nat Med, 2001; 7(11)： 1194.
22. Peters BA, Diaz LA, Polyak K, et al . Contribution of bone marrow-derived endothelial cells to human tumor vasculature [J] . Nat Med, 2005; 11(3)： 261.
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24. Zlotnik A. New insights on the role of CXCR4 in cancer metastasis [J] . J Pathol, 2008; 215(3)： 211.
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27. Miraglia S, Godfrey W, Yin AH, et al . A novelfive-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning [J] . Blood, 1997; 90(12)： 5013.
28. Ricci-Vitiani L, Lombardi DG, Pilozzi E, et al . Identification and expansion of human colon-cancer-initiating cells [J] . Nature, 2007; 445(7123)： 111.
29. Mehra N, Penning M, Maas J, et al . Progenitor marker CD133 mRNA is elevated in peripheral blood of cancer patients with bone metastases [J] . Clin. Cancer Res, 2006; 12(16)： 4859.
30. Corbeil D, Rper K, Hellwig A, et al . The human AC133 hematopoietic stem cell antigen is also expressed in epithelial cells and targeted to plasma membrane protrusions [J] . J Biol Chem, 2000; 275(8)：5512.
  1. 1. 29 Takaishi S, Okumura T, Wang TC. Gastric cancer stem cell [J] . J Clin Oncol, 2008; 26(17)： 2876 30 Houghton J, Stoicov C, Nomura S, et al . Gastric cancer originating from bone marrow-derived cells [J] . Science, 2004; 306(5701)： 1568.
  2. 2. Hanahan D, Weinberg RA. The hallmarks of cancer [J] . Cell, 2000; 100(1)：57.
  3. 3. DAmour KA, Gage FH. Are somatic stem cells pluripotent or lineage-restricted? [J] . Nat Med, 2002; 8(3)： 213.
  4. 4. Singh SK, Hawkins C, Clarke ID, et al . Identification of human brain tumour initiating cells [J] . Nature, 2004; 432(7015)：396.
  5. 5. Lapidot T, Sirard C, Vormoor J, et al . A cell initiating human acute myeloid leukaemia after transplantation into SCID mice [J] . Nature, 1994; 367(6464)： 645.
  6. 6. Park CH, Bergsagel DE, McCulloch EA. Mouse myeloma tumor stem cells: a primary cell culture assay [J] . J Natl Cancer Inst, 1971; 46(2)： 411.
  7. 7. OB(yǎng)rien CA, Pollett A, Gallinger S, et al . A human colon cancer cell capable of initiating tumour growth in immunodeficient mice [J] . Nature, 2006; 445(7123)： 106.
  8. 8. Collins AT, Berry PA, Hyde C, et al . Prospective identification of tumorigenic prostate cancer stem cells [J] . Cancer Res, 2005; 65(23)： 10946.
  9. 9. Suetsugu A, Nagaki M, Aoki H, et al . Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells [J] . Biochem Biophys Res Commun, 2006; 351(4) ∶820.
  10. 10. Yin S, Li J, Hu C, et al . CD133 positive hepatocellular carcinoma cells possess high capacity for tumorigenicity [J] . Int J Cancer, 2007; 120(7)： 1444.
  11. 11. Haraguchi N, Ishikawa K, Kabahara Y, et al . Cancer stem cell and cancer metastasis [J] . Surgery Frontier , 2007; 14(4)： 60.
  12. 12. Hiratsuka S, Nakamura K, Iwai S, et al . MMP-9 induction by vascular endothelial growth factor receptor-1 is involved in lung-specific metastasis [J] . Cancer Cell, 2002; 2(4)： 289.
  13. 13. 張建軍, 劉志明. MMP-9及TIMP-1在甲狀腺癌組織及外周血中的表達(dá)及臨床意義 [J] . 中國(guó)普外基礎(chǔ)與臨床雜志, 2007; 14(4)： 437.
  14. 14. 朱軍華， 陶凱雄， 王國(guó)斌. TNF-α對(duì)肝癌細(xì)胞VEGF和MMP-9表達(dá)的影響 [J] . 中國(guó)普外基礎(chǔ)與臨床雜志, 2005; 12(4)：384.
  15. 15. Müller A, Homey B, Soto H, et al . Involvement of chemokine receptors in breast cancer metastasis [J] . Nature, 2001; 410 (6824)： 50.
  16. 16. Wai PY, Kuo PC. The role of Osteopontin in tumor metastasis [J] . J Surg Res, 2004; 121(2)：228.
  17. 17. Balic M, Lin H, Young L, et al . Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype [J] . Clin Cancer Res, 2006; 12(19)： 5615.
  18. 18. Hugo H, Ackland ML, Blick T, et al . Epithelial-mesenchymal and mesenchymal-epithelial transitions in carcinoma progression [J] . J Cell Physiol, 2007; 213(2)： 374.
  19. 19. Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions [J] . Nat Rev Mol Cell Biol, 2006; 7(2)： 131.
  20. 20. Coussens LM, Tinkle CL, Hanahan D, et al . MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis [J] . Cell, 2000; 103(3)： 481.
  21. 21. Lyden D, Hattori K, Dias S, et al . Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth [J] . Nat Med, 2001; 7(11)： 1194.
  22. 22. Peters BA, Diaz LA, Polyak K, et al . Contribution of bone marrow-derived endothelial cells to human tumor vasculature [J] . Nat Med, 2005; 11(3)： 261.
  23. 23. Kaplan RN, Riba RD, Zacharoulis S, et al . VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche [J] . Nature, 2005; 438(7069)： 820.
  24. 24. Zlotnik A. New insights on the role of CXCR4 in cancer metastasis [J] . J Pathol, 2008; 215(3)： 211.
  25. 25. Hemmati HD, Nakano I, Lazareff JA, et al . Cancerous stem cells can arise from pediatric brain tumors [J] . Proc Natl Acad Sci USA, 2003; 100(25)： 15178.
  26. 26. Stingl J, Eirew P, Ricketson I, et al . Purification and unique properties of mammary epithelial stem cells [J] . Nature, 2006; 439(7079)： 993.
  27. 27. Miraglia S, Godfrey W, Yin AH, et al . A novelfive-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning [J] . Blood, 1997; 90(12)： 5013.
  28. 28. Ricci-Vitiani L, Lombardi DG, Pilozzi E, et al . Identification and expansion of human colon-cancer-initiating cells [J] . Nature, 2007; 445(7123)： 111.
  29. 29. Mehra N, Penning M, Maas J, et al . Progenitor marker CD133 mRNA is elevated in peripheral blood of cancer patients with bone metastases [J] . Clin. Cancer Res, 2006; 12(16)： 4859.
  30. 30. Corbeil D, Rper K, Hellwig A, et al . The human AC133 hematopoietic stem cell antigen is also expressed in epithelial cells and targeted to plasma membrane protrusions [J] . J Biol Chem, 2000; 275(8)：5512.