Tissue around tumor holds key to fighting triple negative breast cancer

A natural substance found in the surrounding tissue of a tumor may be a promising weapon to stop triple negative breast cancer from metastasizing.

A preclinical study published in September 19 by Thomas Jefferson University researchers found that decorin, a well-studied protein known to help halt tumor growth, induces a series of in the surrounding tissue of triple negative tumors that help stop metastasis.

"These findings provide a new paradigm for decorin, with great implications for curbing by inducing new tumor suppressor genes within the tumor microenvironment, and for the discovery of signatures that could eventually help clinical assessment and prognosis," said senior author Renato V. Iozzo, M.D., Professor of Pathology, Anatomy and , at Thomas Jefferson University.

Triple negative breast cancer is the most deadly of breast cancers, with fast-growing tumors, that disproportionately affect younger and African-American women. Today, no such marker is applied in care of triple negative breast cancer, and as a result, patients are all treated the same.

"Originally, we thought that decorin was affecting the tumor, but, surprisingly, decorin affects the so-called tumor microenvironment, where grow and invade, igniting genes to stop such growth," said Dr. Iozzo, who is also a member of Jefferson's Kimmel Cancer Center. "Absence of decorin in the microenvironment could explain metastasis in some patients, where higher levels of the protein may keep cancer from spreading."

In the study, 357 genes were found to be induced by the increased presence of decorin, but more interestingly, the researchers discovered that three of these genes, which were previously unlinked to triple negative breast cancer, were tumor suppressor genes affecting the tumor microenvironment, including Bmp2K, Zc3hav1, and PEG3.

Decorin is a naturally occurring substance in the connective tissue where, among other roles, it helps regulate cell growth by interacting with growth factors and collagen. A decade ago, Dr. Iozzo and his team discovered that decorin, a cell protein, and specifically, a proteoglycan, is increased in the matrix surrounding tumor cells. They also discovered that decorin causes production of a protein, p21, which also can arrest cell growth. However, decorin's role in breast cancer and the mechanism behind its anti-tumor properties remained elusive.

For this study, researchers aimed to investigate the impact of decorin in triple negative breast cancer tumors using human cell lines in mice, as well analyze gene expression activity in the tumor microenvironment.

Tumors treated with decorin were found to have a decreased volume of up to 50 percent after 23 days. Using a sophisticated microarray technique, the researchers then analyzed the mouse tumor microenvironment, finding increased expression of 357 genes, three of which are the tumor suppressor genes of interest.

These results demonstrate a novel role for decorin in reduction or prevention of tumor metastases that could eventually lead to improved therapeutics for metastatic breast cancer.

"Here, we have a molecule that can turn a from a bad neighborhood to a clean neighborhood by inducing genes in that neighborhood to stop growth and prevent the tumor from metastasizing," said Dr. Iozzo.

More information: dx.plos.org/10.1371/journal.pone.0045559

Related Stories

New suppressor of common liver cancer

date Dec 15, 2009

Tumor suppressor genes make proteins that help control cell growth. Mutations in these genes that generate nonfunctional proteins can contribute to tumor development and progression. One of the most well-known tumor suppressor ...

Recommended for you

Study finds new potential melanoma drug target

date May 02, 2015

A new treatment for melanoma could be on the horizon, thanks to a finding by a UNC Lineberger Comprehensive Cancer Center-led team. In the study, which was published online today in the journal Clinical Ca ...

Surgery for terminal cancer patients still common

date May 02, 2015

The number of surgeries performed on terminally ill cancer patients has not dropped in recent years, despite more attention to the importance of less invasive care for these patients to relieve symptoms and ...

Study provides comprehensive look at brain cancer treatments

date May 01, 2015

Led by the Translational Genomics Research Institute (TGen) and UC San Francisco (UCSF), a comprehensive genetic review of treatment strategies for glioblastoma brain tumors was published today in the Oxford University Press ...

How artificial tanning can lead to melanoma

date May 01, 2015

Young women may be up on the latest fashions and trends as they prepare for prom season. But what many don't know is that the tan that looks oh-so-good with their dress may be the first step toward skin cancer.

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.