Journal article
The Dynamic Relationship of Breast Cancer Cells and Fibroblasts in Fibronectin Accumulation at Primary and Metastatic Tumor Sites
Cancers, Vol.12(5), p.1270
05/17/2020
DOI: 10.3390/cancers12051270
PMCID: 7281295
PMID: 32429591
Abstract
In breast cancer (BC), tissue stiffening via fibronectin (FN) and collagen accumulation is associated with advanced disease progression at both the primary tumor and metastatic sites. Here, we evaluate FN production in 15 BC cell lines, representing a variety of subtypes, phenotypes, metastatic potentials, and chemotherapeutic sensitivities. We demonstrate that intracellular and soluble FN is initially lost during tumorigenic transformation but is rescued in all lines with epithelial-mesenchymal plasticity (EMP). Importantly, we establish that no BC cell line was able to independently organize a robust FN matrix. Non-transformed mammary epithelial cells were also unable to deposit FN matrices unless transglutaminase 2, a FN crosslinking enzyme, was overexpressed. Instead, BC cells manipulated the FN matrix production of fibroblasts in a phenotypic-dependent manner. In addition, varied accumulation levels were seen depending if the fibroblasts were conditioned to model paracrine signaling or endocrine signaling of the metastatic niche. In the former, fibroblasts conditioned by BC cultures with high EMP resulted in the largest FN matrix accumulation. In contrast, mesenchymal BC cells produced extracellular vesicles (EV) that resulted in the highest levels of matrix formation by conditioned fibroblasts. Overall, we demonstrate a dynamic relationship between tumor and stromal cells within the tumor microenvironment, in which the levels and fibrillarization of FN in the extracellular matrix are modulated during the particular stages of disease progression.
Details
- Title: Subtitle
- The Dynamic Relationship of Breast Cancer Cells and Fibroblasts in Fibronectin Accumulation at Primary and Metastatic Tumor Sites
- Creators
- Sarah Libring - Purdue University West LafayetteAparna Shinde - Purdue University West LafayetteMonica K. Chanda - Purdue University West LafayetteMaryam Nuru - Purdue University West LafayetteHeather George - Purdue University West LafayetteAya M. Saleh - Purdue University West LafayetteAmmara Abdullah - Purdue University West LafayetteTamara L. Kinzer-Ursem - Purdue University West LafayetteSarah Calve - Purdue University West LafayetteMichael K. Wendt - Purdue University West LafayetteLuis Solorio - Purdue University West Lafayette
- Resource Type
- Journal article
- Publication Details
- Cancers, Vol.12(5), p.1270
- DOI
- 10.3390/cancers12051270
- PMID
- 32429591
- PMCID
- 7281295
- NLM abbreviation
- Cancers (Basel)
- ISSN
- 2072-6694
- eISSN
- 2072-6694
- Publisher
- Mdpi
- Number of pages
- 20
- Grant note
- UL1TR002529 / National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Science Award RSG-16-172-01 / American Cancer Society R00CA198929 / National Cancer Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) DP2 AT009833 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 05/17/2020
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984459631202771
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