Binding of trastuzumab to ErbB2 is inhibited by a high pericellular density of hyaluronan.

The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society
Tímea VáradiPeter Nagy

Abstract

Although trastuzumab is an efficient drug, primary and acquired resistance is a challenging problem. The authors have previously shown in mouse xenograft experiments that masking ErbB2 by hyaluronan leads to diminished binding of the antibody and consequent resistance. In the current work, they correlated trastuzumab binding with the pericellular density of hyaluronan in ErbB2-overexpressing human breast cancer samples. A method for quantifying the relative binding of trastuzumab was developed involving constant and low-frequency background subtraction, segmenting the image to membrane and background pixels followed by evaluation of trastuzumab fluorescence, normalized with the expression level of ErbB2, only in the membrane. The normalized binding of trastuzumab showed a negative correlation with the pericellular density of hyaluronan (r = -0.52) with the effect being the most pronounced in the extreme cases (i.e., low and high hyaluronan densities predicted strong and weak binding of trastuzumab, respectively). Removal of hyaluronan by hyaluronidase digestion unmasked the trastuzumab binding epitope of ErbB2 demonstrated by a significantly increased normalized binding of the antibody. The results show that the accumulation of...Continue Reading

References

Mar 31, 2000·Nature Medicine·R A ClynesJ V Ravetch
Aug 28, 2001·Annals of Oncology : Official Journal of the European Society for Medical Oncology·H A LaneN E Hynes
Nov 22, 2001·The Journal of Biological Chemistry·Anthony J Day, Glenn D Prestwich
Nov 22, 2001·The Journal of Biological Chemistry·Bryan P TooleMarkku I Tammi
Mar 22, 2002·Nature·Yotaro IzumiRakesh K Jain
Feb 20, 2003·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Mario WernickeAna Alcestes Morandi
Aug 5, 2003·The Oncologist·Jeffrey S RossKenneth J Bloom
Apr 20, 2004·Cancer Cell·Matthew C FranklinMark X Sliwkowski
Jul 2, 2004·Nature Reviews. Cancer·Bryan P Toole
Apr 22, 2005·The Journal of Biological Chemistry·Yoshinori TakahashiParaskevi Heldin
Jun 9, 2005·Cells, Tissues, Organs·Bryan P TooleShibnath Ghatak
Feb 7, 2006·Cancer Letters·Rita Nahta, Francisco J Esteva
Sep 26, 2006·Pathology Oncology Research : POR·Tamás LôrinczMiklós Szendrôi
Dec 16, 2006·Journal of Cellular Biochemistry·Dai Fukumura, Rakesh K Jain
Oct 4, 2007·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Zsuzsanna Pályi-KrekkPeter Nagy
Nov 6, 2007·The Journal of Biological Chemistry·Paul H Weigel, Paul L DeAngelis
Feb 15, 2008·Breast Cancer Research and Treatment·Elyse E LowerStacy Harman
May 3, 2008·Seminars in Cancer Biology·Naoki Itano, Koji Kimata
May 3, 2008·Cancer Research·I Bernard Weinstein, Andrew Joe
Jun 25, 2008·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Kirsi RillaRaija Tammi
Sep 20, 2008·Experimental Cell Research·Laura Pentassuglia, Douglas B Sawyer
Nov 18, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Serena Di Cosimo, José Baselga
Feb 12, 2009·Current Opinion in Cell Biology·Nancy E Hynes, Gwen MacDonald
Mar 24, 2009·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Bert van der VegtJelle Wesseling
Feb 4, 2010·Nature Reviews. Clinical Oncology·Serena Di Cosimo, José Baselga
Jul 29, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jeff SperindeAllan Lipton
Oct 28, 2010·Molecular Cancer Therapeutics·Curtis B ThompsonGregory I Frost
Dec 8, 2010·Experimental Cell Research·R K SironenV-M Kosma
Dec 9, 2010·International Journal of Cancer. Journal International Du Cancer·Sarah J StorrStewart G Martin
Mar 10, 2011·International Journal of Cancer. Journal International Du Cancer·Hiroshi UrakawaNaoki Ishiguro
Jul 6, 2011·Trends in Cell Biology·Oliver Lieleg, Katharina Ribbeck

❮ Previous
Next ❯

Citations

Oct 5, 2013·Journal of Biochemistry·Paraskevi HeldinKaoru Kahata
Sep 29, 2012·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·John R Couchman, Csilla A Pataki
Mar 14, 2017·Journal of Oncology·Alexandru FilippiMaria-Magdalena Mocanu
Nov 14, 2019·International Journal of Molecular Sciences·Javeria ZaheerSang Moo Lim
Dec 17, 2014·Molecular Cancer Therapeutics·Netai C SinghaH Michael Shepard
Jul 19, 2019·Seminars in Cancer Biology·Ilaria CaonAlberto Passi
Jun 16, 2021·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Sara SantamariaKatia Cortese
Aug 12, 2021·Molecular Therapy Oncolytics·Martí Farrera-SalRamon Alemany
Dec 6, 2019·Molecular Pharmaceutics·Patricia M R PereiraJason S Lewis

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
biopsy
FRET
flow cytometry

Software Mentioned

MATLAB
SPSS
DipImage

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.