Chronic MIF exposure induces mesenchymal epithelial transition.

<p>HS738 cells have A) a fibroblast morphology, which changes B) upon chronic exposure to recombinant MIF. MIF exposure also decreases expression of fibroblast markers by C) mRNA levels by qRT PCR compared to untreated cells and by D) flow cytometry, while increasing expression of epithelial markers EpCam and E-cadherin by E) mRNA levels by qRT PCR compared to untreated cells and by D) flow cytometry. N = 8 and the mean ± standard error are shown as the results of duplicated in multiple experiments. *<i>p</i><0.05.</p

MIF induces proliferation of gastric and colon carcinoma cells.

<p>Tumor-derived gastric and colon supernatants induced proliferation of N87 and Caco-2 cells, which was decreased upon adding A) anti-MIF neutralizing antibodies or anti-CD74 blocking antibodies. B) Chronic exposure of HS738 or N87 cells with recombinant MIF increased proliferation that was sustained after returning cells to regular media for 8 weeks. N = 8 and the mean ± standard error are shown as the results of duplicated in multiple experiments. *<i>p</i><0.05.</p

CD74 is highly expressed in human gastric and colon tumors and on isolated epithelial cells.

<p>CD74 mRNA levels measured by qRT PCR are increased in A) human gastric tumor samples and at higher levels in tissues from patients with nodal involvement, B) human colon tumor samples and at higher levels in tissues from patients with nodal involvement, and on epithelial cells isolated from human gastric and colon tumors in C) a representative flow cytometry plot and D) in compiled flow cytometry data from all samples. N = 8 for D and the mean ± standard error are shown as the results of duplicated in multiple experiments. *<i>p</i><0.05.</p

MIF is highly expressed in gastric and colon tumors and human tissue-derived fibroblasts.

<p>MIF mRNA levels measured by qRT PCR are increased in A) human gastric tumor samples and at higher levels in tissues from patients with nodal involvement, B) human colon tumor samples and at higher levels in tissues from patients with nodal involvement, and C) in the supernatants tumor derived gastric and colon fibroblasts compared to matched normal as measured by Luminex singleplex assay. N = 8 for C and the mean ± standard error are shown as the results of duplicated in multiple experiments. *<i>p</i><0.05.</p

MIF induces pro-tumorigenic signaling.

<p>Chronic MIF treatment induces A) Akt, B) c-Jun, and C) Erk1/2 phosphorylation. N = 8 and the mean ± standard error are shown as the results of duplicated in multiple experiments. *<i>p</i><0.05.</p

Chronic MIF exposure induces HS738 cell transformation.

<p>HS738 chronic exposure to MIF induces A) upregulation of TERT gene expression so similar levels as N87 control cells and B) colony formation in a focus forming assay. N = 8 and the mean ± standard error are shown as the results of duplicated in multiple experiments. *<i>p</i><0.05.</p

PHA-Induced³H-Thymidine Stimulation and Urinary Arsenic (Inorganic + Organic) in Normal Human Blood Donors.

<p>Note: AsB = arseno betaine, MMA⁺⁵ and DMA⁺⁵ also include MMA⁺³ and DMA⁺³.</p><p>PHA-Induced³H-Thymidine Stimulation and Urinary Arsenic (Inorganic + Organic) in Normal Human Blood Donors.</p

Arsenite Suppresses Anti-CD3/Anti-CD28 Naïve HPBMC T cell Differentiation.

<p>Note: DP = double positive; Values shown are the Mean ± SD with *indicating statistical significance at p<.05.</p><p>Arsenite Suppresses Anti-CD3/Anti-CD28 Naïve HPBMC T cell Differentiation.</p

Evaluation of As⁺³ inhibition of HPBMC proliferation.

<p>In panel A, the typical response of 15 donors is shown where there is no inhibition of PHA-induced T cell proliferation. In panel B, 2 donors are shown that were extremely sensitive to low dose (0.1–1 nM) inhibition of the PHA response. Data shown are the Mean ± SD with *p<.05.</p

RORγt expressing cells proliferate in culture with GMF in a class II MHC dependent manner.

<p>CD4⁺ T cells labeled with CFSE and gated on RORγt⁺ cells for representative histograms for <b>A</b>) non-proliferating control, <b>B</b>) CD4⁺ T cells in culture with normal GMF <b>C</b>) CD4⁺ T cells in culture with <i>H. pylori-</i>exposed GMF, <b>D</b>) CD4⁺ T cells in culture with <i>H. pylori-</i>exposed GMF pre-incubated with class II MHC blocking antibodies <b>E</b>) CD4⁺ T cells in culture with cancer GMF <b>F</b>) CD4⁺ T cells in culture with cancer GMF pre-incubated with class II MHC blocking antibodies. <b>G</b>) Compiled data from 3 experiments in triplicate show the percent proliferating cells from CD4⁺ T cells in culture with normal GMF, <i>H. pylori-</i>exposed GMF, and cancer GMF with class II MHC blocking. (n = 9). <b>*</b><i>p</i><0.05 <i>H. pylori</i> treated or cancer and class II MHC blockade.</p