Live-cell Imaging of Tumor Proteolysis: Impact of Cellular and Non-cellular Microenvironment

Overview

Journal Biochim Biophys Acta

Specialties Biochemistry
Biophysics

Date 2011 Aug 23

PMID 21854877

Citations 12

Authors

Jennifer M Rothberg

Mansoureh Sameni

Kamiar Moin

Bonnie F Sloane

Affiliations

Soon will be listed here.

Abstract

Our laboratory has had a longstanding interest in how the interactions between tumors and their microenvironment affect malignant progression. Recently, we have focused on defining the proteolytic pathways that function in the transition of breast cancer from the pre-invasive lesions of ductal carcinoma in situ (DCIS) to invasive ductal carcinomas (IDCs). We use live-cell imaging to visualize, localize and quantify proteolysis as it occurs in real-time and thereby have established roles for lysosomal cysteine proteases both pericellularly and intracellularly in tumor proteolysis. To facilitate these studies, we have developed and optimized 3D organotypic co-culture models that recapitulate the in vivo interactions of mammary epithelial cells or tumor cells with stromal and inflammatory cells. Here we will discuss the background that led to our present studies as well as the techniques and models that we employ. This article is part of a Special Issue entitled: Proteolysis 50 years after the discovery of lysosome.

Citing Articles

Three-Dimensional Models: Biomimetic Tools That Recapitulate Breast Tissue Architecture and Microenvironment to Study Ductal Carcinoma In Situ Transition to Invasive Ductal Breast Cancer.

Shah S, Osuala K, Brock E, Ji K, Sloane B, Mattingly R Cells. 2025; 14(3).

PMID: 39937011 PMC: 11817749. DOI: 10.3390/cells14030220.

Establishment of a 3D co-culture model to investigate the role of primary fibroblasts in ductal carcinoma in situ of the breast.

Sourouni M, Opitz C, Radke I, Kiesel L, Tio J, Gotte M Cancer Rep (Hoboken). 2022; 6(4):e1771.

PMID: 36534078 PMC: 10075300. DOI: 10.1002/cnr2.1771.

On-demand dissolution of modular, synthetic extracellular matrix reveals local epithelial-stromal communication networks.

Valdez J, Cook C, Ahrens C, Wang A, Brown A, Kumar M Biomaterials. 2017; 130:90-103.

PMID: 28371736 PMC: 5461961. DOI: 10.1016/j.biomaterials.2017.03.030.

Zinc finger E-box binding homeobox-1 (Zeb1) drives anterograde lysosome trafficking and tumor cell invasion via upregulation of Na+/H+ Exchanger-1 (NHE1).

Dykes S, Gao C, Songock W, Bigelow R, Vande Woude G, Bodily J Mol Carcinog. 2016; 56(2):722-734.

PMID: 27434882 PMC: 5731239. DOI: 10.1002/mc.22528.

The Arf-like GTPase Arl8b is essential for three-dimensional invasive growth of prostate cancer in vitro and xenograft formation and growth in vivo.

Dykes S, Gray A, Coleman D, Saxena M, Stephens C, Carroll J Oncotarget. 2016; 7(21):31037-52.

PMID: 27105540 PMC: 5058737. DOI: 10.18632/oncotarget.8832.

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