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Mesenchymal stromal cells alone or expressing interferon-beta suppress pancreatic tumors in vivo, an effect countered by anti-inflammatory treatment.

Publication ,  Journal Article
Kidd, S; Caldwell, L; Dietrich, M; Samudio, I; Spaeth, EL; Watson, K; Shi, Y; Abbruzzese, J; Konopleva, M; Andreeff, M; Marini, FC
Published in: Cytotherapy
September 2010

BACKGROUND AIMS: Because of the inflammatory nature and extensive stromal compartment in pancreatic tumors, we investigated the role of mesenchymal stromal cells (MSC) to engraft selectively in pancreatic carcinomas and serve as anti-tumor drug delivery vehicles to control pancreatic cancer progression. METHODS: Human pancreatic carcinoma cells, PANC-1, expressing renilla luciferase were orthotopically implanted into SCID mice and allowed to develop for 10 days. Firefly luciferase-transduced MSC or MSC expressing interferon (IFN)-beta were then injected intraperitoneally weekly for 3 weeks. Mice were monitored by bioluminescent imaging for expression of renilla (PANC-1) and firefly (MSC) luciferase. RESULTS: MSC selectively homed to sites of primary and metastatic pancreatic tumors and inhibited tumor growth (P=0.032). The production of IFN-beta within the tumor site by MSC-IFN-beta further suppressed tumor growth (P=0.0000083). Prior studies indicated that MSC home to sites of inflammation; therefore, we sought to alter the tumor microenvironment through treatment with a potent anti-inflammatory agent. After treatment, inflammation-associated mediators were effectively down-regulated, including NFkappaB, vascular endothelial growth factor (VEGF) and interleukin (IL)-6 as well as chemokines involved in MSC migration (CCL3 and CCL25). Treatment with the anti-inflammatory agent CDDO-Me before and after MSC-IFN-beta injections resulted in reduction of MSC in the tumors and reversed the positive effect of tumor inhibition by MSC-IFN-beta alone (P=0.041). CONCLUSIONS: These results suggest that MSC exhibit innate anti-tumor effects against PANC-1 cells and can serve as delivery vehicles for IFN-beta for the treatment of pancreatic cancer. However, these beneficial effects may be lost in therapies combining MSC with anti-inflammatory agents.

Duke Scholars

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Published In

Cytotherapy

DOI

EISSN

1477-2566

Publication Date

September 2010

Volume

12

Issue

5

Start / End Page

615 / 625

Location

England

Related Subject Headings

  • Transgenes
  • Stromal Cells
  • Pancreatic Neoplasms
  • Neoplasm Transplantation
  • Mice, SCID
  • Mice
  • Mesenchymal Stem Cells
  • Mesenchymal Stem Cell Transplantation
  • Interferon-beta
  • Inflammation
 

Citation

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Kidd, S., Caldwell, L., Dietrich, M., Samudio, I., Spaeth, E. L., Watson, K., … Marini, F. C. (2010). Mesenchymal stromal cells alone or expressing interferon-beta suppress pancreatic tumors in vivo, an effect countered by anti-inflammatory treatment. Cytotherapy, 12(5), 615–625. https://doi.org/10.3109/14653241003631815
Kidd, Shannon, Lisa Caldwell, Martin Dietrich, Ismael Samudio, Erika L. Spaeth, Keri Watson, Yuexi Shi, et al. “Mesenchymal stromal cells alone or expressing interferon-beta suppress pancreatic tumors in vivo, an effect countered by anti-inflammatory treatment.Cytotherapy 12, no. 5 (September 2010): 615–25. https://doi.org/10.3109/14653241003631815.
Kidd S, Caldwell L, Dietrich M, Samudio I, Spaeth EL, Watson K, et al. Mesenchymal stromal cells alone or expressing interferon-beta suppress pancreatic tumors in vivo, an effect countered by anti-inflammatory treatment. Cytotherapy. 2010 Sep;12(5):615–25.
Kidd, Shannon, et al. “Mesenchymal stromal cells alone or expressing interferon-beta suppress pancreatic tumors in vivo, an effect countered by anti-inflammatory treatment.Cytotherapy, vol. 12, no. 5, Sept. 2010, pp. 615–25. Pubmed, doi:10.3109/14653241003631815.
Kidd S, Caldwell L, Dietrich M, Samudio I, Spaeth EL, Watson K, Shi Y, Abbruzzese J, Konopleva M, Andreeff M, Marini FC. Mesenchymal stromal cells alone or expressing interferon-beta suppress pancreatic tumors in vivo, an effect countered by anti-inflammatory treatment. Cytotherapy. 2010 Sep;12(5):615–625.
Journal cover image

Published In

Cytotherapy

DOI

EISSN

1477-2566

Publication Date

September 2010

Volume

12

Issue

5

Start / End Page

615 / 625

Location

England

Related Subject Headings

  • Transgenes
  • Stromal Cells
  • Pancreatic Neoplasms
  • Neoplasm Transplantation
  • Mice, SCID
  • Mice
  • Mesenchymal Stem Cells
  • Mesenchymal Stem Cell Transplantation
  • Interferon-beta
  • Inflammation