Inorganic arsenic-related changes in the stromal tumor microenvironment in a prostate cancer cell-conditioned media

Model Joseph J Shearer, Eric A. Wold, Charles S. Umbaugh, Cheryl F. Lichti, Carol L. Nilsson, Marxa L. Figueiredo

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: The tumor microenvironment plays an important role in the progression of cancer by mediating stromal-epithelial paracrine signaling, which can aberrantly modulate cellular proliferation and tumorigenesis. Exposure to environmental toxicants, such as inorganic arsenic (iAs), has also been implicated in the progression of prostate cancer. oBjective: The role of iAs exposure in stromal signaling in the tumor microenvironment has been largely unexplored. Our objective was to elucidate molecular mechanisms of iAs-induced changes to stromal signaling by an enriched prostate tumor microenvironment cell population, adipose-derived mesenchymal stem/stromal cells (ASCs). results: ASC-conditioned media (CM) collected after 1 week of iAs exposure increased prostate cancer cell viability, whereas CM from ASCs that received no iAs exposure decreased cell viability. Cytokine array analysis suggested changes to cytokine signaling associated with iAs exposure. Subsequent proteomic analysis suggested a concentration-dependent alteration to the HMOX1/THBS1/TGFβ signaling pathway by iAs. These results were validated by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting, confirming a concentration dependent increase in HMOX1 and a decrease in THBS1 expression in ASC following iAs exposure. Subsequently, we used a TGFβ pathway reporter construct to confirm a decrease in stromal TGFβ signaling in ASC following iAs exposure. conclusions: Our results suggest a concentration-dependent alteration of stromal signaling: specifically, attenuation of stromal-mediated TGFβ signaling following exposure to iAs. Our results indicate iAs may enhance prostate cancer cell viability through a previously unreported stromal-based mechanism. These findings indicate that the stroma may mediate the effects of iAs in tumor progression, which may have future therapeutic implications.

Original languageEnglish (US)
Pages (from-to)1009-1015
Number of pages7
JournalEnvironmental Health Perspectives
Volume124
Issue number7
DOIs
StatePublished - Jul 1 2016

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Tumor Microenvironment
Arsenic
Conditioned Culture Medium
Prostatic Neoplasms
Mesenchymal Stromal Cells
Cell Survival
Paracrine Communication
Cytokines
Environmental Exposure
Reverse Transcriptase Polymerase Chain Reaction
Proteomics
Prostate
Neoplasms
Carcinogenesis
Western Blotting
Cell Proliferation

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Public Health, Environmental and Occupational Health

Cite this

Shearer, M. J. J., Wold, E. A., Umbaugh, C. S., Lichti, C. F., Nilsson, C. L., & Figueiredo, M. L. (2016). Inorganic arsenic-related changes in the stromal tumor microenvironment in a prostate cancer cell-conditioned media. Environmental Health Perspectives, 124(7), 1009-1015. https://doi.org/10.1289/ehp.1510090

Inorganic arsenic-related changes in the stromal tumor microenvironment in a prostate cancer cell-conditioned media. / Shearer, Model Joseph J; Wold, Eric A.; Umbaugh, Charles S.; Lichti, Cheryl F.; Nilsson, Carol L.; Figueiredo, Marxa L.

In: Environmental Health Perspectives, Vol. 124, No. 7, 01.07.2016, p. 1009-1015.

Research output: Contribution to journalArticle

Shearer, MJJ, Wold, EA, Umbaugh, CS, Lichti, CF, Nilsson, CL & Figueiredo, ML 2016, 'Inorganic arsenic-related changes in the stromal tumor microenvironment in a prostate cancer cell-conditioned media', Environmental Health Perspectives, vol. 124, no. 7, pp. 1009-1015. https://doi.org/10.1289/ehp.1510090
Shearer, Model Joseph J ; Wold, Eric A. ; Umbaugh, Charles S. ; Lichti, Cheryl F. ; Nilsson, Carol L. ; Figueiredo, Marxa L. / Inorganic arsenic-related changes in the stromal tumor microenvironment in a prostate cancer cell-conditioned media. In: Environmental Health Perspectives. 2016 ; Vol. 124, No. 7. pp. 1009-1015.
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