scholarly journals C-Reactive Protein and Breast Cancer: New Insights from Old Molecule

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Shilpa Balaji Asegaonkar ◽  
Balaji Narayanrao Asegaonkar ◽  
Unmesh Vidyadhar Takalkar ◽  
Suresh Advani ◽  
Anand Pandurang Thorat

Recently an association between breast cancer and inflammation has emerged as the seventh hallmark of cancer. Chronic inflammation is a key contributor in the development and progression of carcinogenesis. Inflammatory pathways play an important role in the causation of breast cancer. C-reactive protein (CRP) an acute-phase reactant inflammatory protein is synthesized in hepatocytes in response to cytokines that are released from leucocytes within the tumor microenvironment. Several epidemiological studies appraised an association of CRP with breast cancer risk with inconsistent findings. Elevated levels at the time of diagnosis of breast cancer indicate aggressiveness of the tumor. CRP is also a well-established independent prognostic marker. Breast cancer survivors with the state of chronic inflammation are at risk of recurrence and metabolic disturbances. CRP lowering agents along with chemotherapeutic drugs will improve the survival of breast cancer patients. Also, it is a risk predictor for subsequent cardiotoxicity in patients receiving chemotherapy. The present review is aimed at elucidating the role of C-reactive protein, as an inflammatory risk marker and prognostic predictor of breast cancer. It also focuses on conflicting views on the role of CRP in breast cancer and its impact on therapeutic interventions.

2018 ◽  
Vol 52 (7) ◽  
pp. 545-551 ◽  
Author(s):  
Catherine M Sabiston ◽  
Carsten Wrosch ◽  
Andrée L Castonguay ◽  
Benjamin D Sylvester

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Nicholas Parchim ◽  
Wei Wang ◽  
Takayuki Iriyama ◽  
Chen Liu ◽  
Athar H Siddiqui ◽  
...  

Preeclampsia (PE) is a serious pregnancy disease characterized by hypertension and proteinuria. Despite intensive research efforts, the underlying cause of PE remains a mystery. PE is, however, associated with abnormalities of the immune system. Here we report that the levels of C-reactive protein (CRP), an important acute phase reactant, were significantly elevated in the plasma of human with PE at the third trimester. Next, we found that CRP protein levels in the placentas of PE patients were also significantly increased compared to controls. In an effort to determine the exact role of elevated CRP in PE, we infused CRP into pregnant mice. We found that injection of CRP into pregnant mice induced hypertension (170 mmHg mean systolic vs. 125 mmHg mean systolic control; p<0.05) and proteinuria (25 mg/ug vs 12 mg/ug vehicle; p<0.05), indicating the direct role of CRP in PE. CRP is known to bind with phosphocholine on damaged cell membranes. Recent studies identified that neurokinin B (NKB), a placental enriched neuropeptide and known pathogenic molecule for PE, is phosphocholinated. This posttranslational modification increases its stability and enhances NKB-mediated receptor activation. These findings raise an intriguing hypothesis that CRP may bind with NKB coupled to NK3R activation and contribute to PE. To test this hypothesis, we conducted a pulldown assay, and we found that CRP bound with NKB. Next, using a cellular invasion assay, we revealed that CRP decreased invasion of human trophoblast cells (0.7 to 0.07 invasion index, p<0.05), while treatment with an NK3R selective antagonist, SB222200, ameliorated this shallow invasion. Finally, we provided in vivo evidence that inhibition of NK3R by SB222200 or knockdown of NK3R by specific siRNA in a potent nanoparticle delivery system significantly reduced CRP-induced hypertension and proteinuria in pregnant mice (170 mmHg mean systolic CRP-injected vs. 130 mmHg mean systolic siRNA NK3R; p<0.05 and proteinuria 25 mg/ug vs. 15 mg/ug; p<0.05). Overall, our findings demonstrate that elevated CRP contributes to PE and NKB/NK3R is a novel mechanism underlying CRP-mediated shallow invasion and disease development. These studies suggest novel pathogenic biomarkers and innovative therapeutic targets for PE.


2012 ◽  
Vol 5 (11 Supplement) ◽  
pp. B87-B87
Author(s):  
Anne Dee ◽  
Roberta McKean-Cowdin ◽  
Anne McTiernan ◽  
Richard N. Baumgartner ◽  
Kathy B. Baumgartner ◽  
...  

2020 ◽  
pp. 104365962092653
Author(s):  
Thaddeus W. W. Pace ◽  
Terry A. Badger ◽  
Chris Segrin ◽  
Alla Sikorskii ◽  
Tracy E. Crane

Introduction: To date, no study has explored associations between objective stress-related biomarkers (i.e., inflammatory markers, diurnal rhythm of cortisol) and health-related quality of life (HRQOL) in Latina breast cancer survivors and their informal caregivers (i.e., family, friends). Method: This cross-sectional feasibility study assessed saliva C-reactive protein, saliva diurnal cortisol rhythm (cortisol slope), and self-reported HRQOL (psychological, physical, and social domains) in 22 Latina survivor–caregiver dyads. Feasibility was defined as ≥85% samples collected over 2 days (on waking, in afternoon, and in evening). Associations between biomarkers and HRQOL were examined with correlational analyses. Results: Collection of saliva was feasible. Strongest associations were observed between survivor evening cortisol (as well as cortisol slope) and fatigue, a component of physical HRQOL. Discussion: Associations presented may help promote investigations of mechanisms linking stress-related biomarkers and HRQOL in Latina breast cancer survivor–caregiver dyads, which will facilitate development of culturally congruent interventions for this underserved group.


2011 ◽  
Vol 129 (2) ◽  
pp. 485-494 ◽  
Author(s):  
Adriana Villaseñor ◽  
Anita Ambs ◽  
Rachel Ballard-Barbash ◽  
Kathy B. Baumgartner ◽  
Anne McTiernan ◽  
...  

2014 ◽  
Vol 40 (11) ◽  
pp. S64
Author(s):  
J. Meneses Echavez ◽  
R. Ramírez Vélez ◽  
E. González Jímenez ◽  
M.J. Sanchéz Pérez ◽  
E. Molina Montes

1995 ◽  
Vol 310 (1) ◽  
pp. 143-148 ◽  
Author(s):  
D Zhang ◽  
S L Jiang ◽  
D Rzewnicki ◽  
D Samols ◽  
I Kushner

The combination of interleukin 6 (IL-6) and interleukin 1 (IL-1) synergistically induces the human acute-phase reactant, C-reactive protein (CRP) in Hep3B cells. While previous studies have indicated that IL-6 induces transcription of CRP, the mode of action of IL-1 has not been clearly defined. It has been suggested that the effect of IL-1 might be post-transcriptional, exerted through the 5′-untranslated region (5′-UTR). To evaluate the role of IL-1 in CRP gene expression, we studied the effects of interleukin-6 (IL-6) and interleukin-1 beta (IL-1 beta) on both the endogenous CRP gene and on transfected CRP-CAT constructs in Hep3B cells. In kinetic studies of the endogenous CRP gene, IL-1 beta alone had no effect on CRP mRNA levels, but when added to IL-6, synergistically enhanced both CRP mRNA levels and transcription, as determined by Northern-blot analyses and nuclear run-on studies. IL-6 alone and the combination of [IL-1 beta + IL-6] each induced increases in mRNA levels roughly comparable with observed increases in transcription. These findings indicate that the effect of IL-1 beta on CRP expression is exerted largely at the transcriptional level in this system. This conclusion was confirmed by studies in Hep3B cells transiently transfected with CRP-CAT constructs, each containing 157 bp of the CRP 5′-flanking region but differing in the length of the 5′-UTR from 104 bp to 3 bp. All constructs responded in the same way; IL-6, but not IL-1 beta, induced significant chloramphenicol acetyltransferase (CAT) expression which was synergistically enhanced 2- to 3-fold by IL-1 beta. These results indicate that IL-1 beta stimulates transcriptional events in the presence of IL-6 and that the upstream 157 bases of the CRP promoter contain elements capable of both IL-6 induction and the synergistic effect of IL-1 beta on transcription.


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