Journal article
Autocrine Fibronectin Inhibits Breast Cancer Metastasis
Molecular cancer research, Vol.16(10), pp.1579-1589
10/01/2018
DOI: 10.1158/1541-7786.MCR-18-0151
PMCID: PMC6511995
PMID: 29934326
Abstract
Both epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) are linked to metastasis via their ability to increase invasiveness and enhance tumor-initiating capacity. Growth factors, cytokines, and chemotherapies present in the tumor microenvironment (TME) are capable of inducing EMT, but the role of the extracellular matrix (ECM) in this process remains poorly understood. Here, a novel tessellated three-dimensional (3D) polymer scaffolding is used to produce a fibrillar fibronectin matrix that induces an EMT-like event that includes phosphorylation of STAT3 and requires expression of beta 1 integrin. Consistent with these findings, analysis of the METABRIC dataset strongly links high-level fibronectin (FN) expression to decreased patient survival. In contrast, in vitro analysis of the MCF-10A progression series indicated that intracellular FN expression was associated with nonmetastatic cells. Therefore, differential bioluminescent imaging was used to track the metastasis of isogenic epithelial and mesenchymal cells within heterogeneous tumors. Interestingly, mesenchymal tumor cells do not produce a FNmatrix and cannot complete themetastatic process, even when grown within a tumor containing epithelial cells. However, mesenchymal tumor cells form FN-containing cellular fibrils capable of supporting the growth and migration of metastatic-competent tumor cells. Importantly, depletion of FN allows mesenchymal tumor cells to regain epithelial characteristics and initiate in vivo tumor growth within a metastatic microenvironment.
Implications: In contrast to the tumor-promoting functions of fibronectin within the ECM, these data suggest that autocrine fibronectin production inhibits the metastatic potential of mesenchymal tumor cells. (C) 2018 AACR.
Details
- Title: Subtitle
- Autocrine Fibronectin Inhibits Breast Cancer Metastasis
- Creators
- Aparna Shinde - Purdue University West LafayetteSarah Libring - Purdue University West LafayetteAktan Alpsoy - Purdue University West LafayetteAmmara Abdullah - Purdue University West LafayetteJames A. Schaber - Purdue University West LafayetteLuis Solorio - Purdue University West LafayetteMichael K. Wendt - Purdue University West Lafayette
- Resource Type
- Journal article
- Publication Details
- Molecular cancer research, Vol.16(10), pp.1579-1589
- Publisher
- Amer Assoc Cancer Research
- DOI
- 10.1158/1541-7786.MCR-18-0151
- PMID
- 29934326
- PMCID
- PMC6511995
- ISSN
- 1541-7786
- eISSN
- 1557-3125
- Number of pages
- 11
- Grant note
- R01CA207751; R00CA198929 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R00CA198929 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P30CA023168 / Purdue Center for Cancer Research via an NCI RSG-CSM130259 / American Cancer Society
- Language
- English
- Date published
- 10/01/2018
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984460327902771
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