Open Access

P53 regulates the migration of mesenchymal stromal cells in response to the tumor microenvironment through both CXCL12-dependent and -independent mechanisms

  • Authors:
    • Siang-Yo Lin
    • Sonia C. Dolfi
    • Sohrab Amiri
    • Jaidong Li
    • Tulin Budak-Alpdogan
    • Kuo-Chieh Lee
    • Christopher Derenzo
    • Debabrata Banerjee
    • John Glod
  • View Affiliations

  • Published online on: September 23, 2013     https://doi.org/10.3892/ijo.2013.2109
  • Pages: 1817-1823
  • Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Mesenchymal stromal cells (MSCs) are multipotent fibroblast-like cells located in the bone marrow that localize to areas of tissue damage including wounds and solid tumors. Within the tumor microenvironment, MSCs adopt the phenotype of carcinoma-associated fibroblasts (CAFs) and stimulate tumor growth. Production of the chemokine CXCL12, also known as stromal cell-derived factor 1 (SDF-1), by MSCs is required for their in vitro migration in response to tumor cells and has also been implicated in stimulation of tumor growth. The tumor suppressor p53 regulates cellular migration, CXCL12 production and the promotion of tumor growth by carcinoma-associated fibroblasts (CAFs). We investigated the role of p53 in MSC migration to tumors. P53 inhibits the migration of MSCs in response to tumor cells in conjunction with a decrease in CXCL12 transcription. Conversely, decreased p53 activity leads to enhanced MSC migration. Interestingly, increased p53 activity inhibits MSC migration even in the context of high concentrations of exogenous CXCL12. These data show that stromal p53 status impacts the recruitment of MSCs to solid tumors through both regulation of CXCL12 production as well as other mechanisms. Stromal p53 may influence other important aspects of tumor biology such as tumor growth and metastasis through mechanisms distinct from CXCL12.
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December 2013
Volume 43 Issue 6

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

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APA
Lin, S., Dolfi, S.C., Amiri, S., Li, J., Budak-Alpdogan, T., Lee, K. ... Glod, J. (2013). P53 regulates the migration of mesenchymal stromal cells in response to the tumor microenvironment through both CXCL12-dependent and -independent mechanisms. International Journal of Oncology, 43, 1817-1823. https://doi.org/10.3892/ijo.2013.2109
MLA
Lin, S., Dolfi, S. C., Amiri, S., Li, J., Budak-Alpdogan, T., Lee, K., Derenzo, C., Banerjee, D., Glod, J."P53 regulates the migration of mesenchymal stromal cells in response to the tumor microenvironment through both CXCL12-dependent and -independent mechanisms". International Journal of Oncology 43.6 (2013): 1817-1823.
Chicago
Lin, S., Dolfi, S. C., Amiri, S., Li, J., Budak-Alpdogan, T., Lee, K., Derenzo, C., Banerjee, D., Glod, J."P53 regulates the migration of mesenchymal stromal cells in response to the tumor microenvironment through both CXCL12-dependent and -independent mechanisms". International Journal of Oncology 43, no. 6 (2013): 1817-1823. https://doi.org/10.3892/ijo.2013.2109