Progesterone receptor activation downregulates GATA3 by transcriptional repression and increased protein turnover promoting breast tumor growth

Pancreatic cancer (PC) ranks twelfth in frequency of diagnosis but is the fourth leading cause of cancer related deaths with a 5 year survival rate of less than 7 percent. This poor prognosis occurs because the early stages of PC are often asymptomatic. Over-expression of several growth factors, most notably vascular endothelial growth factor (VEGF), has been implicated in PC resulting in dysfunctional signal transduction pathways and the facilitation of tumor growth, invasion and metastasis. Hepatocyte growth factor (HGF) acts via the Met receptor and has also received research attention with ongoing efforts to develop treatments to block the Met receptor and its signal transduction pathways. Macrophage-stimulating protein (MSP), and its receptor Ron, is also recognized as important in the etiology of PC but is less well studied. Although the angiotensin II (AngII)/AT1 receptor system is best known for mediating blood pressure and body water/electrolyte balance, it also facilitates tumor vascularization and growth by stimulating the expression of VEGF. A metabolite of AngII, angiotensin IV (AngIV) has sequence homology with the “hinge regions” of HGF and MSP, key structures in the growth factor dimerization processes necessary for Met and Ron receptor activation. We have developed AngIV-based analogs designed to block dimerization of HGF and MSP and thus receptor activation. Norleual has shown promise as tested utilizing PC cell cultures. Results indicate that cell migration, invasion, and pro-survival functions were suppressed by this analog and tumor growth was significantly inhibited in an orthotopic PC mouse model.

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Mu-opioid receptor activation promotes in vitro and in vivo tumor growth in head and neck squamous cell carcinoma

Life Sciences ◽

10.1016/j.lfs.2021.119541 ◽

2021 ◽

Vol 278 ◽

pp. 119541

Author(s):

Aysegul Gorur ◽

Miguel Patiño ◽

Hideaki Takahashi ◽

German Corrales ◽

Curtis R. Pickering ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Tumor Growth ◽

Cell Carcinoma ◽

Head And Neck ◽

Opioid Receptor ◽

Receptor Activation ◽

Mu Opioid Receptor ◽

Mu Opioid

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Hormonal Factors and Breast Tumor Proliferation: Do Factors that Affect Cancer Risk also Affect Tumor Growth?

Breast Cancer Research and Treatment ◽

10.1023/b:brea.0000025402.70958.3e ◽

2004 ◽

Vol 85 (2) ◽

pp. 133-142 ◽

Cited By ~ 11

Author(s):

Nina Oestreicher ◽

Emily White ◽

Kathleen E. Malone ◽

Peggy L. Porter

Keyword(s):

Cancer Risk ◽

Tumor Growth ◽

Breast Tumor ◽

Tumor Proliferation ◽

Hormonal Factors

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Investigating New Therapeutic Strategies Targeting Hyperinsulinemia's Mitogenic Effects in a Female Mouse Breast Cancer Model

Endocrinology ◽

10.1210/en.2012-2263 ◽

2013 ◽

Vol 154 (5) ◽

pp. 1701-1710 ◽

Cited By ~ 21

Author(s):

Ran Rostoker ◽

Keren Bitton-Worms ◽

Avishay Caspi ◽

Zila Shen-Orr ◽

Derek LeRoith

Keyword(s):

Breast Cancer ◽

Tumor Growth ◽

Breast Tumor ◽

Experimental Studies ◽

Tumor Development ◽

Treated Group ◽

Tumor Growth Rate ◽

Breast Cancer Patients ◽

Mitogenic Effect

Abstract Epidemiological and experimental studies have identified hyperinsulinemia as an important risk factor for breast cancer induction and for the poor prognosis in breast cancer patients with obesity and type 2 diabetes. Recently it was demonstrated that both the insulin receptor (IR) and the IGF-IR mediate hyperinsulinemia's mitogenic effect in several breast cancer models. Although IGF-IR has been intensively investigated, and anti-IGF-IR therapies are now in advanced clinical trials, the role of the IR in mediating hyperinsulinemia's mitogenic effect remains to be clarified. Here we aimed to explore the potential of IR inhibition compared to dual IR/IGF-IR blockade on breast tumor growth. To initiate breast tumors, we inoculated the mammary carcinoma Mvt-1 cell line into the inguinal mammary fat pad of the hyperinsulinemic MKR female mice, and to study the role of IR, we treated the mice bearing tumors with the recently reported high-affinity IR antagonist-S961, in addition to the well-documented IGF-IR inhibitor picropodophyllin (PPP). Although reducing IR activation, with resultant severe hyperglycemia and hyperinsulinemia, S961-treated mice had significantly larger tumors compared to the vehicle-treated group. This effect maybe secondary to the severe hyperinsulinemia mediated via the IGF-1 receptor. In contrast, PPP by partially inhibiting both IR and IGF-IR activity reduced tumor growth rate with only mild metabolic consequences. We conclude that targeting (even partially) both IR and IGF-IRs impairs hyperinsulinemia's effects in breast tumor development while simultaneously sparing the metabolic abnormalities observed when targeting IR alone with virtual complete inhibition.

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Antibiotic-induced disturbances of the gut microbiota result in accelerated breast tumor growth

iScience ◽

10.1016/j.isci.2021.103012 ◽

2021 ◽

Vol 24 (9) ◽

pp. 103012

Author(s):

Alastair M. McKee ◽

Benjamin M. Kirkup ◽

Matthew Madgwick ◽

Wesley J. Fowler ◽

Christopher A. Price ◽

...

Keyword(s):

Gut Microbiota ◽

Tumor Growth ◽

Breast Tumor

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Photothermal Conjugated Polymer Nanoparticles for Suppressing Breast Tumor Growth by Regulating TRPA1 Ion Channels

Advanced Healthcare Materials ◽

10.1002/adhm.202102506 ◽

2021 ◽

pp. 2102506

Author(s):

Boying Li ◽

Shuxi Ren ◽

Dong Gao ◽

Ning Li ◽

Manman Wu ◽

...

Keyword(s):

Ion Channels ◽

Tumor Growth ◽

Breast Tumor ◽

Conjugated Polymer ◽

Polymer Nanoparticles ◽

Conjugated Polymer Nanoparticles

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Systemic Platelet-activating Factor Receptor Activation Augments Experimental Lung Tumor Growth and Metastasis

Cancer Growth and Metastasis ◽

10.4137/cgm.s14501 ◽

2014 ◽

Vol 7 ◽

pp. CGM.S14501 ◽

Cited By ~ 15

Author(s):

Patrick C. Hackler ◽

Sarah Reuss ◽

Raymond L. Konger ◽

Jeffrey B. Travers ◽

Ravi P. Sahu

Keyword(s):

Lung Cancer ◽

Tumor Growth ◽

Cancer Progression ◽

Lung Tumor ◽

Platelet Activating Factor ◽

Receptor Activation ◽

Dependent Manner ◽

Melanoma Tumor ◽

Tumor Growth And Metastasis ◽

The Impact

Pro-oxidative stressors including cigarette smoke (CS) generate novel lipids with platelet-activated factor-receptor (PAF-R) agonistic activity mediate systemic immunosuppression, one of the most recognized events in promoting carcinogenesis. Our previous studies have established that these oxidized-PAF-R-agonists augment murine B16F10 melanoma tumor growth in a PAF-R-dependent manner because of its effects on host immunity. As CS generates PAF-R agonists, the current studies sought to determine the impact of PAF-R agonists on lung cancer growth and metastasis. Using the murine Lewis Lung Carcinoma (LLC1) model, we demonstrate that treatment of C57BL/6 mice with a PAF-R agonist augments tumor growth and lung metastasis in a PAF-R-dependent manner as these findings were not seen in PAF-R-deficient mice. Importantly, this effect was because of host rather than tumor cells PAF-R dependent as LLC1 cells do not express functional PAF-R. These findings indicate that experimental lung cancer progression can be modulated by the PAF system.

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