By Anna C. Greene, PhD, NETRF Chief Scientific Officer
Scientists are discovering that where a tumor grows in the body may influence how it behaves. A new study, supported in part by the Neuroendocrine Tumor Research Foundation (NETRF), provides important insights into how small intestinal neuroendocrine tumors (SI-NETs) develop and spread.
The research, conducted at the University of California, San Francisco and published in Clinical Cancer Research, used an advanced technology called spatial transcriptomics to better understand how tumor cells behave in different parts of the body. This approach allows scientists to study which genes are active in tumor cells while also seeing exactly where those cells are located within the tissue.
Small intestinal neuroendocrine tumors often appear in several places at once, a condition known as multifocal disease. Doctors have long observed that tumors in different locations can behave differently, but the biological reasons for this have remained unclear.
Key Takeaways
- Researchers identified four types of tumor cells in small intestinal neuroendocrine tumors, each linked to where the cells are located in the body.
- Tumor cells behave differently depending on their local environment, such as the intestinal lining, lymph nodes, or mesentery.
- The study identified HTR1D as an important serotonin receptor active in these tumors.
- These discoveries may help guide future diagnostic tools and targeted treatments for neuroendocrine tumors.
Tumor Cells Change Depending on Their Location
To investigate how tumor location affects tumor biology, researchers analyzed tumor samples from four patients with multifocal SI-NETs. They discovered that tumor cells fall into four main groups based on where they are located in the body.
Tumors in the intestinal lining (Mucosal subtype)
Cells located in the lining of the intestine showed gene activity associated with higher metabolic activity and a greater proportion of proliferating cells. Interestingly, these cells looked very similar across separate tumors, even in different patients.
Tumors in the mesentery (Mesenteric subtype)
Some tumor deposits develop in the mesentery, the fatty tissue that holds the intestines in place. These tumor cells showed strong signals related to nerve communication and serotonin signaling.
Tumors in lymph nodes (Lymphatic subtype)
Cells that spread to nearby lymph nodes appeared to be more mobile and less tightly attached to surrounding tissue, which may help them spread.
Tumors deeper in the intestinal wall (Deep subtype)
Cells found deeper in the intestinal wall showed gene activity related to interactions with the surrounding structural tissue.
Together, these findings suggest that the local environment surrounding tumor cells helps shape how those cells behave.
Serotonin May Influence More Than Symptoms
Neuroendocrine tumors are known for producing serotonin, a hormone that can cause symptoms such as flushing and diarrhea.
What is new in this study is the suggestion that serotonin may also help influence how some tumors behave. The researchers identified a serotonin receptor, HTR1D, that appears to play an important role in small intestinal neuroendocrine tumors, particularly in certain tumor subtypes. This finding may help scientists better understand how tumor cells respond to serotonin and how those signals could affect tumor growth or spread.
The research team also examined medical records from 169 patients with SI-NETs. They observed that patients who had taken certain antidepressants that increase serotonin activity were more likely to have tumors in the mesentery.
Importantly, this finding does not mean that these medications cause tumor growth. More research is needed, and patients should never stop or change prescribed medications without speaking with their doctor.
Instead, the finding points to serotonin signaling as an important area for future research.
What This Could Mean for Future Treatments
The study also identified several molecules that may represent possible targets for new treatments. These include HTR1D, along with signaling molecules such as CXCR4, MDK (midkine), and NCL (nucleolin) which help tumor cells communicate with surrounding tissues. Researchers also observed SSTR1 activity, a somatostatin receptor that could help explain why some patients respond to broader-acting somatostatin drugs.
By identifying the biological signals that influence tumor growth and spread, researchers hope to develop more personalized and effective therapies for people living with neuroendocrine tumors.
In the Researcher’s Own Words
“Our study reveals important features of small intestinal neuroendocrine tumors. We discovered new hormone and chemical signaling pathways that appear to play a key role in both the symptoms patients experience and how these tumors grow and behave. We hope these findings will lead to improved ways to diagnose them and the development of more effective treatments for patients.”
— Dr. Eric Nakakura, MD, PhD
Professor of Surgery, University of California, San Francisco
Advancing Research for Patients
Studies like this help scientists better understand the complex biology of neuroendocrine tumors. By learning how tumor cells interact with their surrounding environment, researchers can identify new opportunities for earlier diagnosis and more targeted treatments.
At NETRF, we are committed to funding innovative research that brings us closer to better treatments and improved outcomes for patients living with neuroendocrine cancer.
Read the full study: Spatial Transcriptomics Reveals Location-Specific Tumor Cell Subtypes and Signaling within Multifocal Small Intestinal Neuroendocrine Tumors (Clinical Cancer Research).
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