• 重慶醫(yī)科大學(xué)附屬第一醫(yī)院肝膽外科( 重慶 400016);

目的 　檢測(cè)腫瘤細(xì)胞上清液對(duì)成纖維細(xì)胞的激活情況及激活后血管內(nèi)皮生長(zhǎng)因子-A（VEGF-A）表達(dá)的變化規(guī)律。
方法 　MTT法檢測(cè)普通培養(yǎng)液、含轉(zhuǎn)化生長(zhǎng)因子-β1（TGF-β1）的普通培養(yǎng)液以及腫瘤細(xì)胞上清液組成的條件培養(yǎng)液對(duì)成纖維細(xì)胞生長(zhǎng)情況的影響，用RT-PCR、Western blot及免疫組織化學(xué)法檢測(cè)不同培養(yǎng)條件下成纖維細(xì)胞的α-平滑肌肌動(dòng)蛋白（α-SMA）與VEGF-A的表達(dá)。
結(jié)果 　腫瘤細(xì)胞上清液對(duì)成纖維細(xì)胞的生長(zhǎng)有一定的促進(jìn)作用。含TGF-β1的普通培養(yǎng)液比普通培養(yǎng)液更有利于成纖維細(xì)胞轉(zhuǎn)化為肌成纖維細(xì)胞，并且能維持肌成纖維細(xì)胞的表型，但是二者均不表達(dá)VEGF-A；條件培養(yǎng)液能促進(jìn)成纖維細(xì)胞穩(wěn)定表達(dá)α-SMA和VEGF-A，二者在培養(yǎng)后第1天均開(kāi)始表達(dá)，第3天表達(dá)量達(dá)到峰值，第3天以后表達(dá)穩(wěn)定。
結(jié)論 　腫瘤細(xì)胞上清液能夠有效、穩(wěn)定地激活成纖維細(xì)胞為肌成纖維細(xì)胞，成纖維細(xì)胞的激活程度影響VEGF-A的表達(dá)，二者均具有最佳的激活時(shí)間點(diǎn)，并且最佳時(shí)間點(diǎn)相一致，最佳激活點(diǎn)的成纖維細(xì)胞有望成為一種可用于移植的促進(jìn)血管重建的細(xì)胞。

引用本文： 肖衡,杜成友,羅詩(shī)樵,劉定志,潘龍. 腫瘤細(xì)胞上清液對(duì)成纖維細(xì)胞表型轉(zhuǎn)變及血管內(nèi)皮生長(zhǎng)因子-A 表達(dá)的影響. 中國(guó)普外基礎(chǔ)與臨床雜志, 2012, 19(2): 129-134. doi: 復(fù)制

版權(quán)信息： ?四川大學(xué)華西醫(yī)院華西期刊社《中國(guó)普外基礎(chǔ)與臨床雜志》版權(quán)所有，未經(jīng)授權(quán)不得轉(zhuǎn)載、改編

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3. Viacava P, Naccarato AG, Bocci G, et al. Angiogenesis and VEGF expression in pre-invasive lesions of the human breast[J]. J Pathol, 2004, 204(2)：140-146.
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5. Shao J, Sheng GG, Mifflin RC, et al. Roles of myofibroblasts in prostaglandin E2-stimulated intestinal epithelial proliferation and angiogenesis[J]. Cancer Res, 2006, 66(2)：846-855.
6. Silzle T, Randolph GJ, Kreutz M, et al. The fibroblast：sentinel cell and local immune modulator in tumor tissue[J]. Int J Cancer, 2004, 108(2)：173-180.
7. Fukumura D, Xavier R, Sugiura T, et al. Tumor induction of VEGF promoter activity in stromal cells[J]. Cell, 1998, 94(6)： 715-725.
8. Turner N, Grose R. Fibroblast growth factor signalling：from development to cancer[J]. Nat Rev Cancer, 2010, 10(2)：116-129.
9. Rizzino A, Kazakoff P, Ruff E, et al. Regulatory effects of cell density on the binding of transforming growth factor β, epidermal growth factor, platelet-derived growth factor, and fibroblast growth factor[J]. Cancer Res, 1988, 48(15)：4266-4271.
10. Bhowmick NA, Neilson EG, Moses HL. Stromal fibroblasts in cancer initiation and progression[J]. Nature, 2004, 432(7015)： 332-337.
11. Masur KS, Dewal HS, Dinh TT, et al. Myofibroblasts differentiate from fibroblasts when plated at low density[J]. Proc Natl Acad Sci USA, 1996, 93(9)：4219-4223.
12. Sonoshita M, Takaku K, Sasaki N, et al. Acceleration of intestinal polyposis through prostaglandin receptor EP2 in ApcΔ716 knockout mice[J]. Nat Med, 2001, 7(9)：1048-1051.
13. Seno H, Oshima M, IshikawaTO, et al. Cyclooxygenase 2- and prostaglandin E2 receptor EP2-dependent angiogenesis in ApcΔ716 mouse intestinal polyps[J]. Cancer Res, 2002, 62：506.
14. Puca R, Nardinocchi L, D’Orazi G. Regulation of vascular endothelial growth factor expression by homeodomain-interacting protein kinase-2[J]. J Exp Clin Cancer Res, 2008, 27：22.
  1. 1. Meyer-Ter-Vehn T, Gebhardt S, Sebald W, et al. p38 inhibitors prevent TGF-β-induced myofibroblast transdifferentiation in human tenon fibroblasts[J]. Invest Ophthalmol Vis Sci, 2006, 47(4)：1500-1509.
  2. 2. Ishida Y, Gao JL, Murphy PM. Chemokine receptor CX3CR1 mediates skin woundhealingby promoting macrophageand fibroblast accumulation and function[J]. J Immunol, 2008, 180(1)：569-579.
  3. 3. Viacava P, Naccarato AG, Bocci G, et al. Angiogenesis and VEGF expression in pre-invasive lesions of the human breast[J]. J Pathol, 2004, 204(2)：140-146.
  4. 4. Xouri G, Christian S. Origin and function of tumor stroma fibroblasts[J]. Semin Cell Dev Biol, 2010, 21(1)：40-46.
  5. 5. Shao J, Sheng GG, Mifflin RC, et al. Roles of myofibroblasts in prostaglandin E2-stimulated intestinal epithelial proliferation and angiogenesis[J]. Cancer Res, 2006, 66(2)：846-855.
  6. 6. Silzle T, Randolph GJ, Kreutz M, et al. The fibroblast：sentinel cell and local immune modulator in tumor tissue[J]. Int J Cancer, 2004, 108(2)：173-180.
  7. 7. Fukumura D, Xavier R, Sugiura T, et al. Tumor induction of VEGF promoter activity in stromal cells[J]. Cell, 1998, 94(6)： 715-725.
  8. 8. Turner N, Grose R. Fibroblast growth factor signalling：from development to cancer[J]. Nat Rev Cancer, 2010, 10(2)：116-129.
  9. 9. Rizzino A, Kazakoff P, Ruff E, et al. Regulatory effects of cell density on the binding of transforming growth factor β, epidermal growth factor, platelet-derived growth factor, and fibroblast growth factor[J]. Cancer Res, 1988, 48(15)：4266-4271.
  10. 10. Bhowmick NA, Neilson EG, Moses HL. Stromal fibroblasts in cancer initiation and progression[J]. Nature, 2004, 432(7015)： 332-337.
  11. 11. Masur KS, Dewal HS, Dinh TT, et al. Myofibroblasts differentiate from fibroblasts when plated at low density[J]. Proc Natl Acad Sci USA, 1996, 93(9)：4219-4223.
  12. 12. Sonoshita M, Takaku K, Sasaki N, et al. Acceleration of intestinal polyposis through prostaglandin receptor EP2 in ApcΔ716 knockout mice[J]. Nat Med, 2001, 7(9)：1048-1051.
  13. 13. Seno H, Oshima M, IshikawaTO, et al. Cyclooxygenase 2- and prostaglandin E2 receptor EP2-dependent angiogenesis in ApcΔ716 mouse intestinal polyps[J]. Cancer Res, 2002, 62：506.
  14. 14. Puca R, Nardinocchi L, D’Orazi G. Regulation of vascular endothelial growth factor expression by homeodomain-interacting protein kinase-2[J]. J Exp Clin Cancer Res, 2008, 27：22.