Loss of E-cadherin in the vicinity of necrosis in colorectal carcinomas: Association with NFκB expression

  • Authors:
    • Nektaria Simiantonaki
    • Ursula Kurzik-Dumke
    • Georgia Karyofylli
    • Caren Jayasinghe
    • Charles James Kirkpatrick
  • View Affiliations

  • Published online on: August 1, 2007     https://doi.org/10.3892/ijo.31.2.269
  • Pages: 269-275
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Abstract

The transcription factor NFκB regulates the expression of several tumor-related molecules associated with tumor progression and metastasis. However, the precise mechanisms by which its activation mediates these processes in diverse tumors are unknown. In this study we determined the expression of NFκB in various colorectal carcinoma cell lines, in a series of 90 non-metastatic and metastatic colorectal tumors and in an in vitro 3D-spheroid model of HT-29 cells simulating morphological hallmark of these adenocarcinomas, namely neoplastic glandular nests around a necrotic center. We show that the inactive cytoplasmic NFκB form is evidently up-regulated in the tumor epithelium, especially in the metastatic cases, as compared to normal tissue. We found that in situ nuclear NFκB staining is characteristic for cells that are still viable but dissociated from the surrounding cohesive tumor tissue and destined to die. Evidence for a possible association between NFκB expression and loss of cell adhesion mediated by E-cadherin function has been provided in vivo and in vitro using the HT-29 3D-spheroid model. In both cases, we found a strong correlation between activation of NFκB and loss of E-cadherin expression. Considering the fact that cancer cell necrosis plays a crucial role in metastasis, NFκB activation mediated by loss of E-cadherin may represent an essential, even initial event in this process. Furthermore, we present in vitro data implicating LPS, the endotoxin of gram-negative bacteria, in the triggering of NFκB up-regulation. Thus, release of bacterial endotoxin may essentially contribute to the progression of colon cancer in vivo.

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August 2007
Volume 31 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Simiantonaki N, Kurzik-Dumke U, Karyofylli G, Jayasinghe C and Kirkpatrick CJ: Loss of E-cadherin in the vicinity of necrosis in colorectal carcinomas: Association with NFκB expression. Int J Oncol 31: 269-275, 2007.
APA
Simiantonaki, N., Kurzik-Dumke, U., Karyofylli, G., Jayasinghe, C., & Kirkpatrick, C.J. (2007). Loss of E-cadherin in the vicinity of necrosis in colorectal carcinomas: Association with NFκB expression. International Journal of Oncology, 31, 269-275. https://doi.org/10.3892/ijo.31.2.269
MLA
Simiantonaki, N., Kurzik-Dumke, U., Karyofylli, G., Jayasinghe, C., Kirkpatrick, C. J."Loss of E-cadherin in the vicinity of necrosis in colorectal carcinomas: Association with NFκB expression". International Journal of Oncology 31.2 (2007): 269-275.
Chicago
Simiantonaki, N., Kurzik-Dumke, U., Karyofylli, G., Jayasinghe, C., Kirkpatrick, C. J."Loss of E-cadherin in the vicinity of necrosis in colorectal carcinomas: Association with NFκB expression". International Journal of Oncology 31, no. 2 (2007): 269-275. https://doi.org/10.3892/ijo.31.2.269