Globally last year, 18.1 million new cancer cases were diagnosed and 9.6 million people died from cancer according to recent statistics from the World Health Organization (WHO). The American Cancer Society estimates that in the U.S. alone, there will be over 1.7 million new cancer cases, and more than 600,000 deaths due to cancer in 2019.
Cancer is a group of diseases where abnormal cells grow uncontrollably and spread. Metastasis is when cancer spreads to a different part of the body than where it originated. An estimated 90 percent of cancer deaths are due to metastasis. Understanding the biophysics of metastasis can help in the fight against cancer. Recently, Purdue researchers applied cross-disciplinary fields of physics, math and imaging in a study that provides new insights on how breast cancer spreads to bones.
In an April 2019 study published in Scientific Reports, Indiana University Purdue University Indianapolis (IUPUI) researchers discovered that metastatic tumor cells are attracted to osteocytes, and that attraction may be reversible under mechanical stimulation. The research findings of this study may help accelerate new treatment approaches to prevent and even halt breast cancer from spreading to the bone in the future.
Osteocytes are star-shaped bone cells that do not divide that are commonly found in mature bone tissues. They are the most abundant type of cells in mature bones–an estimated 42 billion osteocytes form 23 trillion connections in the skeleton of the average human. Osteoporosis and osteoarthritis are diseases associated with the malfunctioning of osteocytes. The study shows that osteocytes may function as a simulator or inhibitor in exerting an influence on the migratory behavior of breast cancer cells.
The researchers aimed to answer the question of whether mechanical stimulation to osteocytes change the effect on the migration and molecular operations of breast cancer cells. Using a molecular tension sensor and live cell imaging, the team tested their theory by observing the force dynamics of the focal adhesion.
To do this, the team used a biosensor consisting of Förster resonance energy transfer (FRET) based tension sensor module (TSMod) inserted in vinculin, a protein that plays a role in cellular migration. Reducing vinculin in tumor cells promotes migratory behaviors.
Focal adhesions (FAs) are impermanent membrane-associated multi-protein structures that plays a role in the survival, multiplication, and motility of cells. Motility is the ability to move independently using metabolic energy. The researchers transfected breast cancer cells with a vinculin tension sensor and conducted FRET analysis in order to gain an understanding of the forces on focal adhesions of breast cancer cells and osteocytes.
“The results indicate that migratory behaviors of tumor cells are closely linked to tensile forces at focal adhesions, and in response to mechanical stimulation osteocytes toggle their regulation of migration in tumor cells,” wrote the researchers in their report. “This study suggests a critical role for mechanotransduction of bone in tumor metastasis and a novel target of interactions in bone metastatic tumor cells.”
According to the researchers, “The result herein might contribute not only to our basic understanding of tumor growth and migration in the bone microenvironment but also toward developing novel therapies to prevent bone metastasis associated with breast cancer.”
Copyright © 2019 Cami Rosso All rights reserved.
References
Li, Fangjia, Chen, Andy, Reeser, Andrew, Wang, Yue, Fan, Yao, Liu, Shengzhi, Zhao, Xinyu, Prakash, Rahul, Kota, Divya, Li, Bai-Yan, Yokota, Hiroki, Liu, Jing. “Vinculin Force Sensor Detects Tumor-Osteocyte Interactions.” Scientific Reports. April 4, 2019.
Emory Winship Cancer Institute. “How Cancer Spreads (Metastasis).” Retrieved June 13, 2019 from https://www.cancerquest.org/cancer-biology/metastasis
American Cancer Society. “Cancer Facts & Figures 2019.” Retrieved June 13, 2019 from https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2019/cancer-facts-and-figures-2019.pdf
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