期刊论文详细信息
BMC Gastroenterology
Gastric cancer cell supernatant causes apoptosis and fibrosis in the peritoneal tissues and results in an environment favorable to peritoneal metastases, in vitro and in vivo
Hui-Mian Xu1  Feng Li2  Zhi-Feng Miao1  Zhe Sun1  Cheng-Gang Jiang1  Yan Xu1  Fu-Nan Liu1  Zhi-Dong Lv1  Di Na1 
[1] Department of Oncology, The First Affiliated Hospital, China Medical University, Shenyang, 110001, Liaoning Province, China;Department of Cell Biology, China Medical University, Shenyang, 110001, Liaoning Province, China
关键词: Fibrosis;    Apoptosis;    Mesothelial cell;    Stomach neoplasms;    Peritoneal carcinomatosis;   
Others  :  1113102
DOI  :  10.1186/1471-230X-12-34
 received in 2011-07-04, accepted in 2012-04-20,  发布年份 2012
PDF
【 摘 要 】

Background

In this study, we examined effects of soluble factors released by gastric cancer cells on peritoneal mesothelial cells in vitro and in vivo.

Methods

HMrSV5, a human peritoneal mesothelial cell line, was incubated with supernatants from gastric cancer cells. Morphological changes of HMrSV5 cells were observed. Apoptosis of HMrSV5 cells was observed under a transmission electron microscope and quantitatively determined by MTT assay and flow cytometry. Expressions of apoptosis-related proteins (caspase-3, caspase-8, Bax, bcl-2) were immunochemically evaluated.

Results

Conspicuous morphological changes indicating apoptosis were observed in HMrSV5 cells 24 h after treatment with the supernatants of gastric cancer cells. In vivo, peritoneal tissues treated with gastric cancer cell supernatant were substantially thickened and contained extensive fibrosis.

Conclusions

These findings demonstrate that supernatants of gastric cancer cells can induce apoptosis and fibrosis in HMrSV5 human peritoneal mesothelial cells through supernatants in the early peritoneal metastasis, in a time-dependent manner, and indicate that soluble factors in the peritoneal cavity affect the morphology and function of mesothelial cells so that the resulting environment can become favorable to peritoneal metastases.

【 授权许可】

   
2012 Na et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150204013117247.pdf 1459KB PDF download
Figure 5. 35KB Image download
Figure 4. 72KB Image download
Figure 3. 22KB Image download
Figure 2. 51KB Image download
Figure 1. 92KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】
  • [1]Yahiro M, Chung YS, Nishimura S, Inoue T, Sowa M: Fibrosis in the peritoneum induces by scirrhous gastric cancer cells may act as “soil” for peritoneal dissemination. Cancer 1996, 77(Suppl 8):1668-1674.
  • [2]Jayne D: Molecular biology of peritoneal carcinomatosis. Cancer Treat Res 2007, 134:21-33.
  • [3]Kiyasu Y, Kaneshima S, Koga S: Morphogenesis of peritoneal metastasis in human gastric cancer. Cancer Res 1981, 1:1236-1239.
  • [4]Buck RC: Walker 256 tumor implantation in normal and injured peritoneum studied by electron microscopy, scanning electron microscopy, and autoradiography. Cancer Res 1973, 33:3181-3188.
  • [5]Na D, Liu F, Miao Z, Du Z, Xu H: Destruction of gastric cancer cells to mesothelial cells by apoptosis in the early peritoneal metastasis. J Huazhong Univ Sci Technolog Med Sci 2009, 29:163-168.
  • [6]Na D, Liu FN, Miao ZF, Du ZM, Xu HM: Astragalus extract inhibits destruction of gastric cancer cells to mesothelial cells by anti-apoptosis. World J Gastroenterol 2009, 15:570-577.
  • [7]Lv ZD, Na D, Ma XY, Zhao C, Zhao WJ, Xu HM: Human peritoneal mesothelial cell transformation into myofibroblasts in response to TGF-beta1 in vitro. Int J Mol Med 2011, 27:187-193.
  • [8]Lv ZD, Na D, Liu FN, Du ZM, Sun Z, Li Z, Ma XY, Wang ZN, Xu HM: Induction of gastric cancer cell adhesion through transforming growth factor-beta1-mediated peritoneal fibrosis. J Exp Clin Cancer Res 2010, 29:139. BioMed Central Full Text
  • [9]Na D, Lv ZD, Liu FN, Xu Y, Jiang CG, Sun Z, Miao ZF, Li F, Xu HM: Transforming growth factor beta1 produced in autocrine/paracrine manner affects the morphology and function of mesothelial cells and promotes peritoneal carcinomatosis. Int J Mol Med 2010, 26:325-332.
  • [10]Heath RM, Jayne DG, O’Leary R, Morrison EE, Guillou PJ: Tumour-induced apoptosis in human mesothelial cells: a mechanism of peritoneal invasion by Fas Ligand/Fas interaction. Br J Cancer 2004, 90:1437-1442.
  • [11]Chen JY, Chi CW, Chen HL, Wan CP, Yang WC, Yang AH: TNF-alpha renders human peritoneal mesothelial cells sensitive to anti-Fas antibody-induced apoptosis. Nephrol Dial Transplant 2003, 18:1741-1747.
  • [12]Catalan MP, Subirá D, Reyero A, Selgas R, Ortiz-Gonzalez A, Egido J, Ortiz A: Regulation of apoptosis by lethal cytokines in human mesothelial cells. Kidney Int 2003, 64:321-330.
  • [13]Kosaka K, Yashiro M, Sakate Y, Hirakawa K: A synergistic antitumor effect of interleukin-2 addition with CD80 immunogene therapy for peritoneal metastasis of gastric carcinoma. Dig Dis Sci 2007, 52:1946-1953.
  • [14]Li ZR, Wang Z, Zhu BH, He YL, Peng JS, Cai SR, Ma JP, Zhan WH: Association of tyrosine PRL-3 phosphatase protein expression with peritoneal metastasis of gastric carcinoma and prognosis. Surg Today 2007, 37:646-651.
  • [15]Fujiwara Y, Doki Y, Taniguchi H, Sohma I, Takiguchi S, Miyata H, Yamasaki M, Monden M: Genetic detection of free cancer cells in the peritoneal cavity of the patient with gastric cancer: present status and future perspectives. Gastric Cancer 2007, 10:197-204.
  • [16]Mutsaers SE, Wilkosz S: Structure and function of mesothelial cells. Cancer Treat Res 2007, 134:1-19.
  • [17]Yashiro M, Chung YS, Inoue T, Nishimura S, Matsuoka T, Fujihara T, Sowa M: Hepatocyte growth factor (HGF) produced by peritoneal fibroblasts may affect mesothelial cell morphology and promote peritoneal dissemination. Int J Cancer 1996, 67:289-293.
  • [18]Paget S: The distribution of secondary growths in cancer of the breast. Lancet 1889, 1:571-573.
  • [19]Fukasawa M, Yanagihara DL, Rodgers KE, DiZerega GS: The mitogenic activity of peritoneal tissue repair cells: control by growth factors. J Surg Res 1989, 47:45-51.
  • [20]Chegini N: The role of growth factors in peritoneal healing: transforming growth factor beta (TGF-beta). Eur J Surg Suppl 1997, 577:17-23.
  • [21]Iwamoto I, Imada A: Effects of growth factors on proliferation of cultured human peritoneal mesothelial cells. Nippon Jinzo Gakkai Shi 1992, 34:1201-1208.
  • [22]Akedo H, Shinkai K, Mukai M, Mori Y, Tateishi R, Tanaka K, Yamamoto R, Morishita T: Interaction of rat ascites hepatoma cells with cultured mesothelial cell layers: a model for tumor invasion. Cancer Res 1986, 46:2416-2422.
  • [23]Kimura A, Koga S, Kudoh H, Iitsuka Y: Peritoneal mesothelial cell injury factors in rat cancerous ascites. Cancer Res 1985, 45:4330-4333.
  • [24]Heath RM, Jayne DG, O’Leary R, Morrison EE, Guillou PJ: Tumor-induced apoptosis:a novel mechanism of peritoneal invasion. Br J Surg 2000, 87(Suppl 1):14.
  • [25]Thornberry NA, Lazebnik Y: Caspases: enemies within. Science 1998, 281:1312-1316.
  • [26]Krammer PH, Debatin KM: Death receptors in chemotherapy and cancer. Oncogene 2004, 23:2950-2966.
  • [27]Toda S, Shirataki Y: Inhibitory effects of Astragali Radix, a crude drug in Oriental medicines, on lipid peroxidation and protein oxidative modification by copper. J Ethnopharmacol 1999, 68:331-333.
  • [28]Wolter KG, Hsu YT, Smith CL, Nechushtan A, Xi XG, Youle RJ: Movement of Bax from the cytosol to mitochondria during apoptosis. J Cell Biol 1997, 139:1281-1292.
  文献评价指标  
  下载次数:37次 浏览次数:10次