Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Medical Oncology
Published in: Medical Oncology 2/2012

01-06-2012 | Original Paper

Expression of Toll-like receptor 4 and beta 1 integrin in breast cancer

Authors: B. Petricevic, D. Vrbanec, J. Jakic-Razumovic, I. Brcic, D. Rabic, T. Badovinac, E. Ozimec, V. Bali

Published in: Medical Oncology | Issue 2/2012

Login to get access

Abstract

Toll-like receptor (TLR) 4 signaling pathway has been shown to support tumor cell growth in vitro and in vivo. Its stimulation on breast cancer cell lines induces β1 integrin and promotes tumor invasiveness. However, its role in predicting clinical behavior of tumor is not yet clarified. Therefore, we investigated TLR4 and β1 integrin expression on 133 primary breast cancer samples by immunohistochemistry and correlated it with overall survival and disease-free survival of patients as well as with clinicopathological characteristics of the tumor. We found higher β1 integrin expression in invasive lobular cancer in comparison with other tumor types. No significant association of TLR4 and β1 integrin expression with overall survival or disease-free survival was seen. Therefore, we conclude that expression of these markers is of biological interest but appears to be of little additional use as predictive clinical marker.
Literature
1.
O’Neill LA. When signaling pathways collide: positive and negative regulation of toll-like receptor signal transduction. Immunity. 2008;29:12–20.PubMedCrossRef
2.
Huang B, Zhao J, Unkeless JC, Feng ZH, Xiong H. TLR signaling by tumor and immune cells: a double-edged sword. Oncogene. 2008;27(2):218–24.PubMedCrossRef
3.
Ren T, et al. Functional expression of TLR9 is associated to the metastatic potential of human lung cancer cell. Cancer Biol Ther. 2007;6(11):1704–9.PubMedCrossRef
4.
He W, et al. TLR4 signalling promotes immune escape of human lung cancer cells by inducing immunosuppressive cytokines and apoptosis resistance. Mol Immunol. 2007;44(11):2850–9.PubMedCrossRef
5.
Zhang YB, et al. Increased expression of Toll-like receptors 4 and 9 in human lung cancer. Mol Biol Rep. 2009;36(6):1475–81.PubMedCrossRef
6.
Droemann D, et al. Human lung cancer cells express functionally active Toll-like receptor 9. Resp Res. 2005;6:1–10.CrossRef
7.
Kelly MG, et al. TLR-4 signalling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer. Cancer Res. 2006;66(7):3859–68.PubMedCrossRef
8.
Merrell MA, et al. Toll-like receptor 9 agonists promote cellular invasion by increasing matrix metalloproteinase activity. Mol Cancer Res. 2006;4(7):437–47.PubMedCrossRef
9.
Ilvesaro JM, et al. Toll-like receptor 9 agonists stimulate prostate cancer invasion in vitro. Prostate. 2007;67:774–81.PubMedCrossRef
10.
Xie W, et al. Toll-like receptor 2 mediates invasion via activating NF-κB in MDA-MB-231 breast cancer cells. Biochem Biophys Res Commun. 2009;379(4):1027–32.PubMedCrossRef
11.
Salaun B, Coste I, Rissoan MC, Lebecque SJ, Renno T. TLR3 can directly trigger apoptosis in human cancer cells. J Immunol. 2006;176(8):4894–901.PubMed
12.
Zaks-Zilberman M, Zaks TZ, Vogel SN. Induction of proinflammatory and chemokine genes by lipopolysaccharide and paclitaxel (Taxol) in murine and human breast cancer cell lines. Cytokine. 2001;15:156–65.PubMedCrossRef
13.
Stroinigg N, Srivastava MD. Modulation of toll-like receptor 7 and LL-37 expression in colon and breast epithelial cells by human beta-defensin-2. MD Allergy Asthma Proc. 2005;26(4):299–309.
14.
Yang H, et al. Reduced expression of Toll-like receptor 4 inhibits human breast cancer cells proliferation and inflammatory cytokines secretion. J Exp Clin Cancer Res. 2010;29:92–9.PubMed
15.
Gonzalez-Reyes S, et al. Study of TLR3, TLR4 and TLR9 in breast carcinomas and their association with metastasis. BMC Cancer. 2010;10(1):665–74.PubMedCrossRef
16.
Harmey JH, et al. Lipopolysaccharide-induced metastatic growth is associated with increased angiogenesis, vascular permeability and tumor cell invasion. Int J Cancer. 2002;101:415–22.PubMedCrossRef
17.
Wang JH, et al. Endotoxin/lipopolysaccharide activates NF-kappaB and enhances tumor cell adhesion and invasion through a beta 1 integrin-dependent mechanism. J Immunol. 2003;170:795–804.PubMed
18.
Hemler ME, Mannion BA, Berditchievski F. Association of TM4SF proteins with integrins:relevance to cancer. Biochem Biophys Acta. 1996;1287:67–71.PubMed
19.
Varmer JA, Cheresh DA. Integrins and cancer. Curr Opin Cell Biol. 1996;8:724–30.CrossRef
20.
Arai K, Asakura T, Nemir P. Effect of local tumor removal and retained oncolysate on lung metastasis. J Surg Res. 1992;53:30–8.PubMedCrossRef
21.
Watson RW, Redmond HP, McCarthy J, Burke PE, Bouchier-Hayes D. Exposure of the peritoneal cavity to air regulates early inflammatory responses to surgery in a murine model. Br J Surg. 1995;82:1060–5.PubMedCrossRef
22.
Pidgeon GP, et al. The role of endotoxin/lipopolysaccharide in surgically induced tumour growth in a murine model of metastatic disease. Br J Cancer. 1999;81:1311–7.PubMedCrossRef
23.
Ridley AJ. Rho GTPases and cell migration. J Cell Sci. 2001;114(15):2713–22.PubMed
24.
Morini M, et al. The alpha 3 beta 1 integrin is associated with mammary carcinoma cell metastasis, invasion, and gelatinase B (MMP-9) activity. Int J Cancer. 2000;87(3):336–42.PubMedCrossRef
25.
Felding-Habermann B, et al. Involvement of tumor cell integrin alpha v beta 3 in hematogenous metastasis of human melanoma cells. Clin Exp Metastasis. 2002;19(5):427–36.PubMedCrossRef
26.
Hofmann UB, et al. Coexpression of integrin alpha (v) beta3 and matrix metalloproteinase-2 (MMP-2) coincides with MMP-2 activation: correlation with melanoma progression. J Invest Dermatol. 2000;115(4):625–32.PubMedCrossRef
27.
Hofmann UB, Westphal JR, Van Kraats AA, Ruiter DJ, Van Muijen GN. Expression of integrin alpha (v) beta (3) correlates with activation of membrane-type matrix metalloproteinase-1 (MT1-MMP) and matrix metalloproteinase-2 (MMP-2) in human melanoma cells in vitro and in vivo. Int J Cancer. 2000;87(1):12–9.PubMedCrossRef
28.
Miyamoto S, Teramoto H, Gutkind JS, Yamada KM. Integrins can collaborate with growth factors for phosphorylation of receptor tyrosine kinases and MAP kinase activation: roles of integrin aggregation and occupancy of receptors. J Cell Biol. 1996;135:1633–42.PubMedCrossRef
29.
Moro L, et al. Integrins induce activation of EGF receptor: role in MAP kinase induction and adhesion-dependent cell survival. EMBO J. 1998;17(22):6622–32.PubMedCrossRef
30.
Guo W, et al. Beta 4 integrin amplifies ErbB2 signaling to promote mammary tumorigenesis. Cell. 2006;126(3):489–502.PubMedCrossRef
31.
Gambaletta D, et al. Cooperative signaling between alpha (6) beta (4) integrin and ErbB-2 receptor is required to promote phosphatidylinositol 3-kinase-dependent invasion. Biol Chem. 2000;275(14):10604–10.CrossRef
32.
Bill HM, et al. Epidermal growth factor receptor-dependent regulation of integrin-mediated signaling and cell cycle entry in epithelial cells. Mol Cell Biol. 2004;24(19):8586–99.PubMedCrossRef
33.
Yoon SO, Shin S, Lipscomb EA. A novel mechanism for integrin-mediated ras activation in breast carcinoma cells: the alpha 6 beta 4 integrin regulates ErbB2 translation and transactivates epidermal growth factor receptor/ErbB2 signaling. Cancer Res. 2006;66(5):2732–9.PubMedCrossRef
34.
Oshita F, et al. High expression of integrin ß1 and p53 is a greater poor prognostic factor than clinical stage in small-cell lung cancer. Am J Clin Oncol. 2004;27:215–9.PubMedCrossRef
35.
Bottger TC, et al. Prognostic value of immunohistochemical expression of ß-1 integrin in pancreatic carcinoma. Oncology. 1999;56:308–13.PubMedCrossRef
36.
Nikkola J, et al. Integrin chains ß1 and αv as prognostic factors in human metastatic melanoma. Melanoma Res. 2004;14:29–37.PubMedCrossRef
37.
Gui GP, et al. Integrin expression in primary breast cancer and its relation to axillary nodal status. Surgery. 1995;117:102–8.PubMedCrossRef
38.
Jonjic N, Lucin K, Krstulja M, Iternicka Z, Mustac E. Expression of ß-1 integrins on tumor cells of invasive ductal breast carcinoma. Pathol Res Pract. 1993;189:979–84.PubMedCrossRef
39.
Tavassoli FA, Devilee P. World health organisation classification of tumors. Lyon: IARC Press; 2003. p. 26.
40.
Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991;19:403–10.PubMedCrossRef
41.
Taylor CR. The current role of immunohistochemistry in diagnostic pathology. Adv Pathol Lab Med. 1994;7:59–65.
42.
Bartlett JMS, et al. Evaluating HER2 amplification and overexpression in breast cancer. J Pathol. 2001;195:422–8.PubMedCrossRef
43.
Wang EL, et al. High expression of Toll-like receptor 4/myeloid differentiation factor 88 signals correlates with poor prognosis in colorectal cancer. Br J Cancer. 2010;102(5):908–15.PubMedCrossRef
44.
White DE, Muller WJ. Multifaceted roles of integrins in breast cancer metastasis. J Mammary Gland Biol Neoplasia. 2007;12:135–42.PubMedCrossRef
45.
Gonzalez MA, et al. An immunohistochemical examination of the expression of E-cadherin, alpha- and beta/gamma-catenins, and alpha2- and beta1-integrins in invasive breast cancer. J Pathol. 1999;187(5):523–9.PubMedCrossRef
46.
Berry MG, Gui GP, Wells CA, Carpenter R. Integrin expression and survival in human breast cancer. Eur J Surg Oncol. 2004;30(5):484–9.PubMedCrossRef
47.
Diaz LK, et al. Beta4 integrin subunit gene expression correlates with tumor size and nuclear grade in early breast cancer. Mod Pathol. 2005;18(9):1165–75.PubMedCrossRef
48.
Lesniak D, et al. Beta1-integrin circumvents the antiproliferative effects of trastuzumab in human epidermal growth factor receptor-2-positive breast cancer. Cancer Res. 2009;69(22):8620–8.PubMedCrossRef
49.
Friedrichs K, et al. High expression level of alpha 6 integrin in human breast carcinoma is correlated with reduced survival. Cancer Res. 1995;55(4):901–6.PubMed
50.
Bergamaschi A, et al. Extracellular matrix signature identifies breast cancer subgroups with different clinical outcome. J Pathol. 2008;214(3):357–67.PubMedCrossRef
51.
Gasparini G, et al. Vascular integrin alpha (v)beta 3: a new prognostic indicator in breast cancer. Clin Cancer Res. 1998;4(11):2625–34.PubMed
52.
Serre CM, Clezardin P, Frappart L, Boivin G, Delmas PD. Distribution of thrombospondin and integrin alpha V in DCIS, invasive ductal and lobular human breast carcinomas. Analysis by electron microscopy. Virchows Arch. 1995;427(4):365–72.PubMedCrossRef
53.
Lanzafame S, Emmanuele C, Torrisi A. Correlation of alpha 2 beta 1 integrin expression with histological type and hormonal receptor status in breast carcinomas. Pathol Res Pract. 1996;192(10):1031–8.PubMedCrossRef
Metadata
Title
Expression of Toll-like receptor 4 and beta 1 integrin in breast cancer
Authors
B. Petricevic
D. Vrbanec
J. Jakic-Razumovic
I. Brcic
D. Rabic
T. Badovinac
E. Ozimec
V. Bali
Publication date
01-06-2012
Publisher
Springer US
Published in
Medical Oncology / Issue 2/2012
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-011-9885-0

Other articles of this Issue 2/2012

Medical Oncology 2/2012 Go to the issue

Original Paper

Tetramethylpyrazine reverses multidrug resistance in breast cancer cells through regulating the expression and function of P-glycoprotein

Original Paper

Overexpression of Nanog protein is associated with poor prognosis in gastric adenocarcinoma

Original Paper

Carbohydrate antigen 242 highly consists with carbohydrate antigen 19-9 in diagnosis and prognosis of colorectal cancer: study on 185 cases

Case Report

Durable remission of leptomeningeal metastases from hormone-responsive prostate cancer

Original Paper

Her-2 prognostic value in very early-stage breast cancer: a single-institution retrospective analysis

Original Paper

Effect of rs6983267 polymorphism in the 8q24 region and rs4444903 polymorphism in EGF gene on the risk of sporadic colorectal cancer in Iranian population
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits