Factors associated with obesity alter matrix remodeling in breast cancer tissues.

Yang Zhang,Boyang Lyu,Lauren E Hillers Ziemer,Zhiyi Liu,Irene Georgakoudi,Lisa M Arendt,Fatma Kucuk Baloglu

doi:10.1117/1.jbo.25.1.014513

Yang Zhang, Boyang Lyu + Show 5 more

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https://doi.org/10.1117/1.jbo.25.1.014513

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Abstract

.Obesity is associated with a higher risk of developing breast cancer and with worse disease outcomes for women of all ages. The composition, density, and organization of the breast tissue stroma are also known to play an important role in the development and progression of the disease. However, the connections between obesity and stromal remodeling are not well understood. We sought to characterize detailed organization features of the collagen matrix within healthy and cancerous breast tissues acquired from mice exposed to either a normal or high fat (obesity inducing) diet. We performed second-harmonic generation and spectral two-photon excited fluorescence imaging, and we extracted the level of collagen-associated fluorescence (CAF) along with metrics of collagen content, three-dimensional, and two-dimensional organization. There were significant differences in the CAF intensity and overall collagen organization between normal and tumor tissues; however, obesity-enhanced changes in these metrics, especially when three-dimensional organization metrics were considered. Thus, our studies indicate that obesity impacts significantly collagen organization and structure and the related pathways of communication may be important future therapeutic targets.

Highlights

Obesity is a worldwide pandemic, and it is considered as high risk for numerous diseases.[1]
While the distributions for normal breast tissues appear fairly similar independent of the diet to which the mice were exposed to (NN and HN), the shape of the 3-D variance probability density function (PDF) corresponding to tumor tissue from mice fed a high-fat diet (HFD) (HT) is even further weighted toward smaller values when compared to the NT one
Our goal was to assess the impacts of obesity on metrics of collagen organization and structure within the matrix of normal and tumor breast tissues, as assessed by quantitative analysis of high-resolution Second-harmonic generation (SHG) and two-photon excited fluorescence (TPEF) spectroscopic images

Summary

Introduction

Obesity is a worldwide pandemic, and it is considered as high risk for numerous diseases.[1]. Obesity has been shown to affect collagen organization, while diabetes and obesity are broadly

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