Role of fibrillar Tenascin-C in metastatic pancreatic cancer

  • Authors:
    • Jian Chen
    • Zhiyu Chen
    • Ming Chen
    • Dajiang Li
    • Zhihua Li
    • Yan Xiong
    • Jiahong Dong
    • Xiaowu Li
  • View Affiliations

  • Published online on: April 1, 2009     https://doi.org/10.3892/ijo_00000228
  • Pages: 1029-1036
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Abstract

Interaction of cancer cells with stroma cells facilitates tumor progression by rebuilding the existing extracellular matrix (ECM) microenvironment. In the tumor, upregulation of Tenascin-C (Tn-C) expression potentially can alter tumor behavior. However, the molecular mechanisms by which tumor-stroma interactions affect the tumor microenvironment have not been well characterized. In this study, we analyzed the expression of fibrillar Tn-C (fTn-C) in human metastatic pancreatic cancers. After co-culturing two pancreatic cancer cell lines, highly metastatic BxPc3 cells and non-metastatic PaCa2 cells, with stromal fibroblasts (SF), we evaluated the roles of matrix metalloproteinase 2 (MMP-2) activation and SF in promoting Tn-C organization. Next, we evaluated whether fibrillar Tn-C promotes pancreatic cancer cell movement using cell adhesion and migration assays. Finally, we observed the relationship between MMP-2 activation and fTn-C formation in vivo by injecting the BxPc3 and PaCa2 cells into nude mice. We found that fTn-C was increased in metastatic pancreatic cancer. The fTn-C expression correlated with MMP-2 activity. In the in vitro co-culture, fTn-C organization was found only in BxPc3/SF co-cultures, and required the participation of active MMP-2. The fTn-C reduced cell adhesion and promote pancreatic cancer cell migration by decreasing the adhesive interactions between integrin α6β1 and the ECM. The in vivo tumorigenesis analysis showed that the fTn-C formation and active MMP-2 were significantly increased in the BxPc3 tumors, compared to the PaCa2 tumors. These results demonstrate that Tn-C deposition into the ECM requires participation of active MMP-2 and SF. The deposited Tn-C could promote pancreatic cancer progression.

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April 2009
Volume 34 Issue 4

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

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APA
Chen, J., Chen, Z., Chen, M., Li, D., Li, Z., Xiong, Y. ... Li, X. (2009). Role of fibrillar Tenascin-C in metastatic pancreatic cancer. International Journal of Oncology, 34, 1029-1036. https://doi.org/10.3892/ijo_00000228
MLA
Chen, J., Chen, Z., Chen, M., Li, D., Li, Z., Xiong, Y., Dong, J., Li, X."Role of fibrillar Tenascin-C in metastatic pancreatic cancer". International Journal of Oncology 34.4 (2009): 1029-1036.
Chicago
Chen, J., Chen, Z., Chen, M., Li, D., Li, Z., Xiong, Y., Dong, J., Li, X."Role of fibrillar Tenascin-C in metastatic pancreatic cancer". International Journal of Oncology 34, no. 4 (2009): 1029-1036. https://doi.org/10.3892/ijo_00000228