We've updated our Privacy Policy to make it clearer how we use your personal data. We use cookies to provide you with a better experience. You can read our Cookie Policy here.


New Clues for the Role of Fibroblasts in Stomach Cancer

A confocal microscopy image of a fibroblast showing the nucleus, mitochondria and actin cytoskeleton.
Fibroblast. Credit: Guy Jones, Matthew Dreher, Brad Wood/ NCI Center for Cancer Research
Listen with
Register for free to listen to this article
Thank you. Listen to this article using the player above.

Want to listen to this article for FREE?

Complete the form below to unlock access to ALL audio articles.

Read time: 1 minute

Fibroblast cells play key roles in the repair of damaged tissue and in pathological scarring. Now, researchers at Vanderbilt University Medical Center have uncovered evidence of their direct involvement in the development of gastric cancer.

These findings, published in the journal Gastroenterology, could lead to novel interventions to prevent cancer of the stomach, the third leading cause of cancer deaths worldwide after lung and colorectal malignancies.

Until recently it has been difficult to identify which cells are involved in the steps leading to gastric cancer, notably the development of precancerous stomach lesions called metaplasia, and later, dysplasia, the appearance of abnormal cells.

“Our studies demonstrated that particular subsets of fibroblasts present in the stomachs of patients with metaplasia and cancer can promote transition of precancerous metaplasia towards dysplasia,” said James Goldenring, MD, PhD, the Paul W. Sanger Professor of Surgery and vice chair for research in the Section of Surgical Sciences.

Want more breaking news?

Subscribe to Technology Networks’ daily newsletter, delivering breaking science news straight to your inbox every day.

Subscribe for FREE

In 1999 Goldenring and his colleagues were the first to describe spasmolytic polypeptide-expressing metaplasia (SPEM), a lineage of metaplastic cells in the stomach that develop from normal protein-secreting cells after damage to the stomach lining. Chronic persistence of these cells can lead to the development of gastric cancer.

For several years they have been using metaplastic and dysplastic gastroids, three-dimensional cultures of epithelial cells isolated from the stomach lining of mice and humans, to identify the characteristics of precancerous stem cell populations.

In the latest study, the researchers isolated four distinct subsets of fibroblasts from the stroma, the tissue surrounding the stomach lining, in healthy people and those with gastric cancer.

One subset of fibroblasts was expanded in patients with metaplasia and cancer compared to healthy controls. When cocultured with SPEM gastroids, these metaplasia- or cancer-derived fibroblasts induced disordered growth, loss of metaplastic cell markers, and an increase in dysplastic cell markers, indicative of the transition of metaplastic cells towards cancer.

Culturing metaplastic gastroids with conditioned media from the laboratory dishes in which these fibroblasts were grown also promoted the dysplastic transition, suggesting that dysplastic progression can be accelerated by factors secreted by the fibroblasts in proximity to metaplastic epithelial cells in the stomach lining.

These findings indicate that SPEM lineage cells under the influence of altered fibroblast populations may evolve to dysplasia without going through intermediate steps.

While further study is needed, targeting this subset of fibroblasts and the factors they secrete may be an effective way to block the progression from precancerous stomach lesions to gastric cancer, the researchers concluded.

Reference: Lee SH, Contreras Panta EW, Gibbs D, et al. Apposition of fibroblasts with metaplastic gastric cells promotes dysplastic transition. Gastroenterology. 2023:S0016-5085(23)00731-X. doi: 10.1053/j.gastro.2023.04.038

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.