Next Article in Journal
Advance Care Planning in Glioblastoma Patients
Previous Article in Journal
Identifying Cancer Driver Genes Using Replication-Incompetent Retroviral Vectors
Previous Article in Special Issue
Reduced Contractility and Motility of Prostatic Cancer-Associated Fibroblasts after Inhibition of Heat Shock Protein 90
Article Menu

Export Article

Open AccessFeature PaperArticle
Cancers 2016, 8(11), 100; doi:10.3390/cancers8110100

TβRIII Expression in Human Breast Cancer Stroma and the Role of Soluble TβRIII in Breast Cancer Associated Fibroblasts

1
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
2
Department of Bioengineering, University of California San Francisco, San Francisco, CA 94117, USA
3
Department of Cancer Biology, Vanderbilt University, Nashville, TN 37232, USA
4
Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA
5
Research Medicine, Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37232, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Huey-Jen Lin
Received: 30 August 2016 / Revised: 4 October 2016 / Accepted: 20 October 2016 / Published: 4 November 2016
(This article belongs to the Special Issue Cancer-Associated Fibroblasts)
View Full-Text   |   Download PDF [3614 KB, uploaded 4 November 2016]   |  

Abstract

The TGF-β pathway plays a major role in tumor progression through regulation of epithelial and stromal cell signaling. Dysfunction of the pathway can lead to carcinoma progression and metastasis. To gain insight into the stromal role of the TGF-β pathway in breast cancer, we performed laser capture microdissection (LCM) from breast cancer patients and reduction mammoplasty patients. Microdissected tumor stroma and normal breast stroma were examined for gene expression. Expression of the TGF-β type III receptor (TGFBR3) was greatly decreased in the tumor stroma compared to control healthy breast tissue. These results demonstrated a 44-fold decrease in TGFBR3 mRNA in tumor stroma in comparison to control tissue. We investigated publicly available databases, and have identified that TGFBR3 mRNA levels are decreased in tumor stroma. We next investigated fibroblast cell lines derived from cancerous and normal breast tissue and found that in addition to mRNA levels, TβRIII protein levels were significantly reduced. Having previously identified that cancer-associated fibroblasts secrete greater levels of tumor promoting cytokines, we investigated the consequences of soluble-TβRIII (sTβRIII) on fibroblasts. Fibroblast conditioned medium was analyzed for 102 human secreted cytokines and distinct changes in response to sTβRIII were observed. Next, we used the fibroblast-conditioned medium to stimulate human monocyte cell line THP-1. These results indicate a distinct transcriptional response depending on sTβRIII treatment and whether it was derived from normal or cancerous breast tissue. We conclude that the effect of TβRIII has distinct roles not only in cancer-associated fibroblasts but that sTβRIII has distinct paracrine functions in the tumor microenvironment. View Full-Text
Keywords: TGFBR3; TβRIII; Cancer-Associated-Fibroblasts (CAFs); tumor microenvironment; cancer stroma; Betaglycan TGFBR3; TβRIII; Cancer-Associated-Fibroblasts (CAFs); tumor microenvironment; cancer stroma; Betaglycan
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Jovanović, B.; Pickup, M.W.; Chytil, A.; Gorska, A.E.; Johnson, K.C.; Moses, H.L.; Owens, P. TβRIII Expression in Human Breast Cancer Stroma and the Role of Soluble TβRIII in Breast Cancer Associated Fibroblasts. Cancers 2016, 8, 100.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top