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Identification of potential tumor differentiation factor (TDF) receptor from steroid-responsive and steroid-resistant breast cancer cells.

ABSTRACT: Tumor differentiation factor (TDF) is a recently discovered protein, produced by the pituitary gland and secreted into the bloodstream. TDF and TDF-P1, a 20-amino acid peptide selected from the open reading frame of TDF, induce differentiation in human breast and prostate cancer cells but not in other cells. TDF protein has no identified site of action or receptor, and its mechanism of action is unknown. Here, we used TDF-P1 to purify and identify potential TDF receptor (TDF-R) candidates from MCF7 steroid-responsive breast cancer cells and non-breast HeLa cancerous cells using affinity purification chromatography (AP), and mass spectrometry (MS). We identified four candidate proteins from the 70-kDa heat shock protein (HSP70) family in MCF7 cells. Experiments in non-breast HeLa cancerous cells did not identify any TDF-R candidates. AP and MS experiments were validated by AP and Western blotting (WB). We additionally looked for TDF-R in steroid-resistant BT-549 cells and human dermal fibroblasts (HDF-a) using AP and WB. TDF-P1 interacts with potential TDF-R candidates from MCF7 and BT-549 breast cells but not from HeLa or HDF-a cells. Immunofluorescence (IF) experiments identified GRP78, a TDF-R candidate, at the cell surface of MCF7, BT-549 breast cells, and HeLa cells but not HDF-a cells. IF of other HSP70 proteins demonstrated labeling on all four cell types. These results point toward GRP78 and HSP70 proteins as strong TDF-R candidates and suggest that TDF interacts with its receptor, exclusively on breast cells, through a steroid-independent pathway.

SUBMITTER: Sokolowska I

PROVIDER: S-EPMC3265855 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Identification of potential tumor differentiation factor (TDF) receptor from steroid-responsive and steroid-resistant breast cancer cells.

Sokolowska Izabela I Woods Alisa G AG Gawinowicz Mary Ann MA Roy Urmi U Darie Costel C CC

The Journal of biological chemistry 20111130 3

Tumor differentiation factor (TDF) is a recently discovered protein, produced by the pituitary gland and secreted into the bloodstream. TDF and TDF-P1, a 20-amino acid peptide selected from the open reading frame of TDF, induce differentiation in human breast and prostate cancer cells but not in other cells. TDF protein has no identified site of action or receptor, and its mechanism of action is unknown. Here, we used TDF-P1 to purify and identify potential TDF receptor (TDF-R) candidates from M ...[more]

PMID: 22130669

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Project description:Allergic airway inflammation is a chronic inflammatory condition resulting from uncontrolled immune responses to environmental antigens. While it is well-established that allergic immune responses exhibit a high degree of diversity, driven by primary effector cell types like eosinophils, neutrophils, or CD4 T cells with distinct effector signatures, the exact mechanisms responsible for such pathogenesis remain largely elusive. Foxp3+ regulatory T cells (Treg) is an indispensable immune regulator during chronic inflammation including allergic airway inflammation. Emerging evidence suggests that Tregs infiltrating inflamed tissues exhibit distinct phenotypes dependent on the specific tissue sites and can display significant heterogeneity and tissue residency. Whether diverse allergic inflammatory responses in the lung influences infiltrating Treg heterogeneity or Treg lung residency has not previously been explored. We employed an unbiased single-cell RNAseq approach to study lung-infiltrating Tregs in models of eosinophilic and neutrophilic airway inflammation models, in which Tregs are critical immune regulators of inflammation. We found that lung-infiltrating Tregs are highly heterogeneous and that Tregs displaying lung residency phenotypes are significantly different depending on the types of inflammation. Tregs expression of ST2, a receptor for alarmin cytokine IL-33, was predominantly induced by eosinophilic inflammation and by tissue residency. However, Treg-specific ST2 deficiency did not affect the development of eosinophilic allergic inflammation nor the generation of lung resident Tregs. These results uncover a striking heterogeneity among Tregs infiltrating the lungs during allergic airway inflammation. The results also indicate that varying types of inflammation may give rise to phenotypically distinct lung resident Tregs. Thus, the present study underscores a novel mechanism by which inflammatory environments may shape the composition of infiltrating Tregs, allowing them to regulate inflammatory responses through tissue-adapted mechanisms.

Dataset Information

Identification of potential tumor differentiation factor (TDF) receptor from steroid-responsive and steroid-resistant breast cancer cells.

Publications

Identification of potential tumor differentiation factor (TDF) receptor from steroid-responsive and steroid-resistant breast cancer cells.

Similar Datasets

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