Pigment epithelial-derived factor and melanoma differentiation associated gene-7 cytokine gene therapies delivered by adipose-derived stromal/mesenchymal stem cells are effective in reducing prostate cancer cell growth

Olga Cain, Gang Yu, Jeffrey M. Gimble, Marxa L. Figueiredo

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Adipose-derived stromal/mesenchymal stem cells (ASC) have gained interest as promising tools for delivering cancer therapy. Adipose tissue can be obtained readily in amounts sufficient for ASC isolation, which can be expanded rapidly, allowing its use at low passage numbers, and can be transduced by viral and nonviral means. Our goal was to examine the potential of ASC to deliver cytokine gene therapies melanoma differentiation associated gene-7 (MDA-7) or pigment epithelial-derived factor (PEDF) to cancer cells. These novel cytokines are a potent proapoptotic and an antiangiogenesis mediator, respectively, with potential as antitumor agents. Expression of cytokine therapies did not adversely affect ASC biology, and these cells were still able to differentiate and retain normal viability. The ASC cytokine therapies were efficient in reducing tumor cell growth in coculture and also in suppressing in vitro angiogenesis phenotypes. We also observed that ASC retained their innate ability to migrate toward tumor cells in coculture, and this ability could be blocked by inhibition of CXCR4 signaling. The ASC were found to be nontumorigenic in vitro using a soft agar assay, as well as in vivo, utilizing 2 prostate cancer xenograft models. The ASC-MDA7 only reduced tumor growth in the TRAMP-C2-Ras (TC2Ras) prostate cancer model. The ASC-PEDF, however, reduced growth in both the TC2Ras and the PC3 highly aggressive prostate cancer models, and it was able to completely prevent prostate tumor establishment in vivo. In conclusion, ASC expressing PEDF and MDA7 could effectively reduce prostate tumor growth in vivo, suggesting ASC-cytokine therapies might have translational applications, especially the PEDF modality.

Original languageEnglish (US)
Pages (from-to)1112-1123
Number of pages12
JournalStem Cells and Development
Volume21
Issue number7
DOIs
StatePublished - May 1 2012

Fingerprint

Mesenchymal Stromal Cells
Genetic Therapy
Melanoma
Prostatic Neoplasms
Cytokines
Growth
Genes
Neoplasms
Cell- and Tissue-Based Therapy
Coculture Techniques
Prostate
Cell Separation
Heterografts
Antineoplastic Agents
Agar
Cell Biology
Adipose Tissue
Phenotype

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Hematology

Cite this

Pigment epithelial-derived factor and melanoma differentiation associated gene-7 cytokine gene therapies delivered by adipose-derived stromal/mesenchymal stem cells are effective in reducing prostate cancer cell growth. / Cain, Olga; Yu, Gang; Gimble, Jeffrey M.; Figueiredo, Marxa L.

In: Stem Cells and Development, Vol. 21, No. 7, 01.05.2012, p. 1112-1123.

Research output: Contribution to journalArticle

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