4.3 Article

Accumulation of amyloid beta (Aβ) and amyloid precursor protein (APP) in tumors formed by a mouse xenograft model of inflammatory breast cancer

期刊

FEBS OPEN BIO
卷 12, 期 1, 页码 95-105

出版社

WILEY
DOI: 10.1002/2211-5463.13308

关键词

inflammatory breast cancer; xenografts; tumor; amyloid beta; immunostaining

资金

  1. NIH [SC2 GM111149, SC3 GM111171]

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The study found that Aβ peptides are present in breast cancer tumors, distributed in gradients with concentration near blood vessels. Significant presence of amyloid precursor protein (APP) was also detected in tumor samples.
Accumulation of amyloid in breast cancer is a well-known phenomenon, but only immunoglobulin light-chain amyloidosis (AL) or transthyretin (TTR) amyloid had been detected in human breast tumor samples previously. We recently reported that another amyloidogenic peptide, amyloid beta (A beta), is present in an aggregated form in animal and human high-grade gliomas and suggested that it originates systemically from the blood, possibly generated by platelets. To study whether breast cancers are also associated with these A beta peptides and in what form, we used a nude mouse model inoculated with triple-negative inflammatory breast cancer cell (SUM-149) xenografts, which develop noticeable tumors. Immunostaining with two types of specific antibodies for A beta identified the clear presence of A beta peptides associated with (a) carcinoma cells and (b) extracellular aggregated amyloid (also revealed by Congo red and thioflavin S staining). A beta peptides, in both cells and in aggregated amyloid, were distributed in clear gradients, with maximum levels near blood vessels. We detected significant presence of amyloid precursor protein (APP) in the walls of blood vessels of tumor samples, as well as in carcinoma cells. Finally, we used ELISA to confirm the presence of elevated levels of mouse-generated A beta 40 in tumors. We conclude that A beta in inflammatory breast cancer tumors, at least in a mouse model, is always present and is concentrated near blood vessels. We also discuss here the possible pathways of A beta accumulation in tumors and whether this phenomenon could represent the specific signature of high-grade cancers.

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