There are many forms of breast cancer. Some occur at an early age but some develop in middle age or beyond. Some are negatively influenced by hormones but some are positively influenced. Some return while others don’t. Some spread (metastasize), some don’t.
When cancers return (recur) or metastasize, the cancer is said to be of an aggressive nature and is strongly associated with an undesirable long-term outcome. Finding out why some cancers stay gone after treatment while others return or spread is the subject of intense study.
A recent study from the United Kingdom suggests one piece of the puzzle lies in the extracellular matrix (ECM), a sticky fluid that surrounds all cells and holds them together. Another recent study, this one from China, found metastasis is associated with how communications over gap junctions in the ECM between cancer cells and stromal cells (cells of the connective tissue in the organs of the body) influence cancer spread.
Two Genes and Scaffolding
Researchers at The Institute of Cancer Research, London, used latest imaging technologies to observe a protein – laminin – in the ECM that works with other proteins and elements of the ECM to build a scaffold-like structure that surrounds cells and holds them together. The research was done specifically with HER2-positive breast cancer cells (representing approximately 20% of all breast cancer tumor types).
They found two genes – F12 and STC2 – strongly associated with survival of this form of cancer. These genes work in tandem to influence how well cancer cells stick to laminin and stay within the tumor-site scaffolding or escape it to create new tumors elsewhere:
- When F12 activity was high and STC2 activity low, the 10-year survival rate was low (68%).
- When this genetic activity was reversed – F12 low and STC2 high – the 10-year survival rate improved to 90%.
“We found that the activity of two genes which may help control how tightly cells are glued together is linked to breast cancer survival,” said Dr. Paul Huang, leader of the Protein Networks Team at the London institute.
“Survival rates for breast cancer are now much higher than they were a few decades ago, but the disease remains deadly once it has spread round the body. Our study sheds light on how cancer cells unstick themselves from healthy tissue, and it could help pick out women at high risk of their cancer spreading and becoming fatal,” he said.
Gap Junction Communications and Metastasis
A team of researchers from several facilities in China found gap junctions in the ECM between breast cancer tumors and their surrounding microenvironment. This microenvironment is populated with ECM as well as various types of cells that promote health on a cellular level. They found that the more coupling the gap junctions do, the less likely breast cancer cells can escape to form new tumors in other parts of the body.
As with the UK study, the researchers hope more in-depth study of this activity in the ECM will lead to new and more effective ways of determining who is at risk of metastasis. There is also the expectation that knowing more about the details of interaction between cancerous and healthy cells, the ECM, and the gap junctions will lead to more effective and more precisely targeted means of eradicating existing cancer cells and preventing their spread.
Missed Radiation Appointments Increase Risk of Recurrence
When cancer patients are prescribed daily radiation treatments but fail to keep their appointments, the risk of recurrence increases, according to a recent study from the Albert Einstein College of Medicine Montefiore Medical Center in New York City. This study found that missing only two out of a series of daily treatments doubles the rate of cancer recurrence for patients with any of several common types of cancer, including breast cancer.
Given the new findings on the significance of ECM activity and metastasis, missed appointments may allow cancer cells that escape the original tumor site to gain a stronger foothold in an area not touched by the radiation.
Huang, Paul H, et al. "Systematic analysis of tumour cell-extracellular matrix adhesion identifies independent prognostic factors in breast cancer." Oncotarget (Impact Journals, LLC) (2016). Web. 23 Aug. 2016.
Mao, XY, et al. "Gap junction as an intercellular glue: Emerging roles in cancer EMT and metastasis." PubMed. Cancer Letters (Elsevier), Aug. 2016. US National Library of Medicine / National Institutes of Health. Web. 23 Aug. 2016.
Hemphill, Sandy. "Two Missed Radiation Treatments Doubles Cancer Recurrence Rate." babyMed. BabyMed.com, Feb. 2016. Web. 23 Aug. 2016.
By Sandy Hemphill, Contributing Writer, BabyMed