Support for the hypothesis that successful immunotherapy of various cancers can be achieved by inhibiting a progesterone associated immunomodulatory protein

Check, Jerome H.; Dix, Ebony; SanSoucie, Lynn

doi:10.1016/j.mehy.2008.05.042

Cited by 24 publications

(18 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently it was shown that PIBF is up-regulated in undifferentiated proliferating cells (e.g, trophoblast cells) as well as in a set of malignancies [10][11][12][13][14]. Several breast cancers overexpress PIBF compared to normal breast tissues [12]; moreover, MCF-7 breast carcinoma cells produce PIBF independently of progesterone [12].…”

Section: Introductionmentioning

confidence: 99%

Progesterone-induced blocking factor differentially regulates trophoblast and tumor invasion by altering matrix metalloproteinase activity

Halász

Polgar

Berta

et al. 2013

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Invasiveness is a common feature of trophoblast and tumours; however, while tumour invasion is uncontrolled, trophoblast invasion is strictly regulated. Both trophoblast and tumour cells express high levels of the immunomodulatory Progesterone-Induced Blocking Factor (PIBF), therefore, we aimed to test the possibility that PIBF might be involved in invasion. To this aim we used PIBF silenced or PIBF treated trophoblast (HTR8/Svneo, and primary trophoblast) and tumour (HT-1080, A549, HCT116, PC3) cell lines. Silencing of PIBF increased invasiveness as well as MMP-2,-9 secretion of HTR8/SVneo, and decreased those of HT-1080 cells. PIBF induced immediate STAT6 activation in both cell lines. Silencing of IL-4Rα abrogated all the above effects of PIBF, suggesting that invasion-related signalling by PIBF is initiated through the IL-4Rα/PIBF-receptor complex. In HTR-8/SVneo PIBF induced fast, but transient Akt and ERK phosphorylation, whereas in tumour cells PIBF triggered sustained Akt, ERK and late STAT3 activation. The late signalling events might be due to indirect action of PIBF. PIBF induced the expression of EGF and HB-EGF in HT-1080 cells. The STAT3 activating effect of PIBF was reduced in HB-EGF deficient HT-1080 cells, suggesting that PIBF-induced HB-EGF contributes to late STAT3 activation. PIBF binds to the promoters of IL-6, EGF and HB-EGF; however, the protein profile of the protein/DNA complex is different in the two cell lines. We conclude that in tumour cells PIBF induces proteins, which activate invasion signalling, while -based on our previous data -PIBF might control trophoblast invasion by suppressing invasive genes.

show abstract

Section: Introductionmentioning

confidence: 99%

Progesterone-induced blocking factor differentially regulates trophoblast and tumor invasion by altering matrix metalloproteinase activity

Halász

Polgar

Berta

et al. 2013

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

show abstract

“…This led to the hypothesis that the allogeneic stimulus of certain tumor antigens may induce PRs in gamma/delta T cells in the tumor microenvironment leading to PIBF expression and subsequent suppression of NK cytolytic activity and a shift of TH1 to TH2 cytokines similar to the pregnancy state [66]. Through the demonstration of marked palliative effect of PR antagonists for both murine and human cancers (which will be discussed in a later section), data have provided support for the hypothesis that similar to the pregnancy state, PIBF may play a role in allowing cancer cells to escape immune surveillance [67]. A case of acute leukemia and possible lung cancer dramatically responding to mifepristone (a PR antagonist) but without increased levels of PIBF, suggests that it may be the intracytoplasmic location of PIBF that confers immune protection [68].…”

Section: Abstract: Cancer • Growth Factors • Immunosuppression • Infementioning

confidence: 90%

The role of progesterone and the progesterone receptor in human reproduction and cancer

Check

Cohen

2013

Expert Review of Endocrinology & Metabolism

View full text Add to dashboard Cite

Insufficient progesterone, effect possibly more on immune factors rather than adequate endometrial development, can be an easy remedial cause of infertility by simply supplementing the luteal phase with either vaginal or intramuscular or oral (dydrogesterone) progesterone. Progesterone will also help to reduce miscarriage rates when follicle maturing drugs are used for those with regular menses but follicular maturation defects, or women with recurrent miscarriages. One mechanism of action seems to be related to production of an immunomodulatory protein, the progesterone-induced blocking factor either in the cytoplasm or in the circulation. PIBF inhibits cytotoxicity of natural killer cells. Cancer cells may 'borrow' the same mechanism to escape NK cell immunosurveillance. KEYWORDS: cancer • growth factors • immunosuppression • infertility • miscarriage • preterm delivery • progesterone• progesterone receptor • progesterone receptor antagonist • progesterone-induced blocking factor

show abstract

“…Glioblastomas are also highly immunosuppressive [ 26 ], probably through the secretion of immunomodulatory factors such as TGF- β or PIBF [ 27 , 28 ]. Interestingly, the latter causes a marked diminution of Th1/Th2 cells ratio during pregnancy [ 15 , 29 ], leading to an immunosuppressive state, which may provide glioma cells with a mechanism of evasion from organism immune system and facilitate tumor progression [ 30 ]. Given that PIBF is induced by P 4 and modulates different pathways involved in cell growth and inflammation, the aim of this study was to investigate the role of PIBF in cell proliferation, migration, and invasion of U87 and U251 cells derived from human glioblastomas.…”

Section: Introductionmentioning

confidence: 99%

Proliferative and Invasive Effects of Progesterone-Induced Blocking Factor in Human Glioblastoma Cells

Gutiérrez-Rodríguez

Hansberg-Pastor

2017

BioMed Research International

View full text Add to dashboard Cite

Progesterone-induced blocking factor (PIBF) is a progesterone (P4) regulated protein expressed in different types of high proliferative cells including astrocytomas, the most frequent and aggressive brain tumors. It has been shown that PIBF increases the number of human astrocytoma cells. In this work, we evaluated PIBF regulation by P4 and the effects of PIBF on proliferation, migration, and invasion of U87 and U251 cells, both derived from human glioblastomas. PIBF mRNA expression was upregulated by P4 (10 nM) from 12 to 24 h. Glioblastoma cells expressed two PIBF isoforms, 90 and 57 kDa. The content of the shorter isoform was increased by P4 at 24 h, while progesterone receptor antagonist RU486 (10 μM) blocked this effect. PIBF (100 ng/mL) increased the number of U87 cells on days 4 and 5 of treatment and induced cell proliferation on day 4. Wound-healing assays showed that PIBF increased the migration of U87 (12–48 h) and U251 (24 and 48 h) cells. Transwell invasion assays showed that PIBF augmented the number of invasive cells in both cell lines at 24 h. These data suggest that PIBF promotes proliferation, migration, and invasion of human glioblastoma cells.

show abstract

Support for the hypothesis that successful immunotherapy of various cancers can be achieved by inhibiting a progesterone associated immunomodulatory protein

Cited by 24 publications

References 12 publications

Progesterone-induced blocking factor differentially regulates trophoblast and tumor invasion by altering matrix metalloproteinase activity

Progesterone-induced blocking factor differentially regulates trophoblast and tumor invasion by altering matrix metalloproteinase activity

The role of progesterone and the progesterone receptor in human reproduction and cancer

Proliferative and Invasive Effects of Progesterone-Induced Blocking Factor in Human Glioblastoma Cells

Contact Info

Product

Resources

About