Featured Post from ChristianaCare

Researchers Discover That Cancer Stem Cell Populations in Colorectal Cancers Are Diverse, Not Uniform

Apr 4, 2023

4 min

Discovery may lead to more precise treatments for advanced colorectal cancer


Researchers at ChristianaCare’s Cawley Center for Translational Cancer Research at the Helen F. Graham Cancer Center & Research Institute have demonstrated for the first time that microRNA (miRNA) expression leads to a diversity of cancer stem cells within a colorectal cancer tumor. This diversity of cancer cells may explain why advanced colorectal cancer is difficult to treat. Study results have been in the Journal of Stem Cell Research and Therapy.


The findings broaden the understanding of how miRNA expression adds to cancer stem cell diversity and may lead to more precise anti-cancer treatments for patients with advanced colorectal cancer. The research builds on prior discoveries by scientists at the Graham Cancer Center about how cancer stem cell activity contributes to the development and spread of colorectal cancer.


“Our research shows — at least in the laboratory — that there are different subpopulations of cancer stem cells in a tumor, and they may be driving the growth of the cancer,” said Principal Investigator Bruce Boman, M.D., Ph.D., MSPH, FACP, medical director of Cancer Genetics and Stem Cell Biology at the Graham Cancer Center. “In one subpopulation of cancer stem cells, its miRNA will shut down the stem cell genes that are expressed in another subpopulation, and vice versa, within the same tumor.”


From left: ChristianaCare researchers Lynn Opdenaker, Ph.D., Brian Osmond, Bruce Boman, M.D., Ph.D., Chi Zhang, Victoria Hunsu, Caroline Facey, Ph.D. Not pictured Victoria Stark, MS.


The study focused on the composition of cancer stem cells within a colorectal cancer cell line (HT29) in the laboratory setting. Researchers evaluated the different cancer stem cell subpopulations that were identified by examining patterns of miRNA expression in each subpopulation and looking for differences. The researchers found that each of the four diverse subpopulations that were studied (ALDH, LRIG1, CD166 and LGR5) had a different miRNA expression or gene signature.


The researchers found that miRNA expression could inhibit the expression of messenger RNA (mRNA), which carries instructions from the DNA to encode specific proteins within cells. Therefore, miRNA, by controlling gene expression, dictate which proteins are contained in the stem cells. The researchers discovered the miRNA that are upregulated in certain cancer stem cell subpopulations are downregulated in other cancer stem cell subpopulations. In this way, differential miRNA expression leads to cancer stem cell heterogeneity within colorectal tumor tissue.


“It’s an early research finding and needs to be followed up with other experiments, but it has clear relevance to the clinic,” Boman said. “The question is: Can you target the miRNA to make cancer more sensitive to certain treatments? Because we know what the current anti-cancer treatments are targeting, we may be able to modulate or manipulate the cancer, so it becomes more sensitive to the treatment.”


Identification of a network of genes regulated by microRNAs in a cancer stem cell subpopulation.



For more than a decade, ChristianaCare’s researchers have contributed to the understanding of the role that cancer stem cells and miRNA expression play in the development and spread of colorectal cancer. This latest finding builds on earlier discoveries that examined a link between two cellular signaling pathways: retinoic acid (RA) signaling and wingless-related integration site (WNT) signaling, which are dysregulated by different gene mutations in colorectal tumors.


The RA signaling pathway induces growth arrest and differentiation of cancer stem cells. Notably, retinoic acid is effective against other types of cancer such as leukemia. The role of the WNT signaling pathway has an opposite effect on tumor growth. The WNT signaling pathway is activated by a mutation in the APC (adenomatous polyposis coli) gene in about 90% of cases of colorectal cancer. In APC mutant tissue, dysregulated miRNA expression may underlie an imbalance between the RA and WNT signaling, which then leads to intratumoral cancer stem cell heterogeneity. Still, this mechanism that may enable the cancer to proliferate could also provide clues on how to more effectively treat cancer.


“If you’ve got an imbalance between these two signaling pathways, then you’ve likely got a growth driver,” Boman said. “The question is: Can you suppress the WNT signaling and enhance the retinoic acid signaling?”


It may be possible to increase the sensitivity of colorectal cancer to retinoic acid-type drugs, and therapeutically shift the balance between different cancer stem cell subpopulations, thereby suppressing cancer growth. More research is needed to determine how targeted cancer therapies containing retinoic acid-type drugs may be made more effective against advanced cancer.


This research will be presented at the annual meeting of the American Association for Cancer Research in Orlando, Florida, April 14-19.


This research project was supported by a grant from the Lisa Dean Moseley Foundation.

You might also like...

Check out some other posts from ChristianaCare

2 min

Forbes Ranks ChristianaCare Among America’s Best Employers for Women in 2024

ChristianaCare has been recognized as one of America’s Best Employers for Women by Forbes for 2024, marking the first time the company has received this prestigious recognition. In a survey of 150,000 women working for companies of at least 1,000 employees in the U.S., ChristianaCare ranked 150 on the list of 600 employers that were recognized. “This important recognition is a testament to our culture and the remarkable women who have chosen to build meaningful careers at ChristianaCare,” said Chris Cowan, MEd, FABC, ChristianaCare’s Chief Human Resources Officer. “Empowering women to succeed is integral to our culture and strengthens our organization. Together, we’ll continue to advance equity and inclusion in the workplace while transforming health and clinical care.” Forbes partnered with market research firm Statista, which surveyed employees on various aspects such as workplace environment, growth opportunities, compensation, diversity, parental leave, schedule flexibility and family assistance. ChristianaCare continues to cultivate a strong, inclusive, and diverse culture for women inside and outside the company by investing in professional development through its Women’s Employee Network (WEN) and providing a comprehensive benefits package that includes various flexible leave options for employees, including at least 12 weeks of paid parental leave. “Receiving this recognition from Forbes is an honor,” said Pamela Ridgeway, MBA, MA, SPHR, chief diversity officer and vice president of Talent and Acquisition at ChristianaCare. “In addition to offering workplace benefits such as paid maternity and paternity leave, ChristianaCare is firmly committed to empowering and advancing talented individuals within the workplace. Receiving this award for the first time signifies our unwavering dedication to ensuring that every individual has a voice and feels truly valued within our organization.” The Forbes recognition follows other national recognitions of ChristianaCare’s commitment to an inclusive workplace. Earlier this year, Forbes ranked ChristianaCare as one of the best employers for diversity in the U.S. Additionally, Forbes ranked ChristianaCare as the top health care employer for veterans in the United States. Both ChristianaCare’s Wilmington Hospital and Christiana Hospital have been named Leaders in LGBTQIA+ Healthcare Equality since 2012.

2 min

ChristianaCare, Delaware’s Largest Private Employer, Raises Minimum Wage to $16.50 an Hour

ChristianaCare has increased its minimum wage to $16.50 an hour effective July 21, 2024. The new $16.50 per hour minimum wage exceeds federal, Delaware, Maryland, New Jersey and Pennsylvania minimum wage rates. “At ChristianaCare, we are committed to creating health so that people can flourish, and that begins with our caregivers,” said ChristianaCare System Chief Operating Officer Ric Cuming, Ed.D., RN, NEA-BC, FAAN. “By investing in our caregivers and supporting their wellbeing, we support their ability to provide the very best care to our patients." ChristianaCare is the largest private employer in Delaware with nearly 14,000 employees. This is the second time in recent years that ChristianaCare has raised its minimum wage; in 2019, ChristianaCare was among the first health systems in the region to raise its minimum wage to $15/hour. This new increase to ChristianaCare’s minimum wage impacts approximately 850 caregivers who were below or near $16.50/hour. Download "It's important for us to lead by example in paying wages that support the financial wellbeing of our workforce,” said Chris Cowan, MEd, FABC, ChristianaCare’s Chief Human Resources Officer. "Substantially increasing wages is one way we continue to attract and keep top talent at all levels in this highly competitive market. By recognizing the valuable contributions of our caregivers, we can enhance staff retention, boost morale and support an exceptional experience for everyone we serve.” The increase is a part of ChristianaCare’s overall Total Rewards package for its caregivers, which includes a wide variety of benefits and support for caregivers and their families through all stages of life. Learn more about ChristianaCare’s Total Rewards here.

3 min

First in Delaware to Offer MR-Guided Ultrasound for Treatment of Essential and Parkinson’s Tremor

Revolutionary technology gives patients immediate relief from debilitating tremors without the need for invasive surgery. ChristianaCare is the first health care provider in Delaware to offer FDA-approved focused ultrasound treatment for people suffering from essential tremor and Parkinson’s disease. The new option – called MR-guided focused ultrasound – uses sound wave energy to destroy precise areas of brain tissue that is the source of the tremor. No surgical incision or anesthesia is necessary, and many patients experience immediate and significant reduction in tremors, which can make daily activities challenging. Dr. Martello explains that the procedure involves the use of high-frequency sound waves directed with pinpoint precision by magnetic resonance imaging to ablate, or burn, the focal point deep within the brain that is causing tremors. “This minimally invasive technology dramatically improves the lives of patients with essential tremor and tremor-dominant Parkinson’s who haven’t fully responded to traditional treatments,’’ said Justin Martello, M.D., director of the Parkinson’s and Movement Disorders Programs, and Focused Ultrasound Program at ChristianaCare. What is tremor? Tremor is a neurological condition that includes involuntary shaking or trembling movements in one or more parts of the body. It most commonly affects the hands and can make daily tasks such as writing, eating and using a computer or phone extremely difficult. Tremor affects approximately 1% of the population overall and 5% of adults age 60+. It is expected to increasingly impact Delawareans as the state’s population ages. Essential tremor is the most common type of tremor. It can occur at any age but is most common in older adults. Tremor is also the most well-known symptom of Parkinson’s disease. An estimated 1.5 million Americans suffer from Parkinson’s disease, a progressive neurodegenerative disease that affects movement and can also affect speech, balance and cognitive function. A newer, better option for patients who don’t respond to medications The procedure of MR-guided focused ultrasound involves the use of high-frequency sound waves directed with pinpoint precision by magnetic resonance imaging to ablate, or burn, the focal point deep within the brain that is causing tremors. Patients are fitted with a frame affixed to a specialized helmet that combines the focused energy of more than 1,000 high-frequency sonic beams directed through the skull. The treatment does not require cutting through the skull, or radiation, as in gamma knife technology. “Today, there are basically three options for managing tremor,” said Pulak Ray, M.D., of Delaware Neurosurgical Group and associate director of the Focused Ultrasound program. “The first is medication, which is effective and affordable for many patients, but its effectiveness tends to diminish over time. The second is deep-brain stimulation, which is the most invasive and costly treatment option. The newest is MR-guided ultrasound, which tends to be the preferable option for most patients who do not respond well to medication, because it is a simple, non-invasive outpatient procedure that is highly effective, safe and produces instant results.” Benefits of MR-guided Focused Ultrasound MR-guided focused ultrasound reduces tremor immediately, with shorter recovery time, lower risk of side effects and lower associated health care expenses compared to surgical alternatives. This treatment dramatically improves patient experience and quality of life for people with Parkinson’s disease or essential tremor. For many patients, MR-guided ultrasound reduces their dependence on caregivers to assist with activities of daily living. Candidates must first undergo a CT scan to ensure a skull density sufficiently thick to accommodate the procedure. The patient is awake during the procedure and situated within an MRI machine for real-time imaging of the brain. The physician tests the precise location by heating the area, then ensuring the patient is able to control tremors by tracing lines on a spirograph. At that point, the physician then permanently ablates the focal point, usually a sphere a few millimeters in length. “Our team is very excited to bring this technology to Delaware and to open up access to potentially life-changing treatment that until now has required long wait times and significant travel for patients,” said Kim Gannon, M.D., Ph.D., medical director of the comprehensive stroke program and physician executive of Neuroscience Service Line at ChristianaCare. “Many tremor patients have suffered for years or even decades with this debilitating and progressive condition and helping them live a more active and independent lifestyle is extremely rewarding.” MR-guided focused ultrasound is covered by Medicare and most insurance plans.

View all posts
Powered by