How Tumor Oxygen Deficiency Can Indirectly Encourage Colon Cancer Progression

Recent research reveals a surprising connection between oxygen shortages within the tumor environment and the advancement of colon cancer. Traditionally, hypoxia—or low oxygen levels—was thought to suppress tumor growth, leading to treatments aimed at depriving cancer cells of oxygen. However, new findings indicate that localized hypoxia can actually promote tumor progression through a complex cellular mechanism.

A multi-institutional study, including scientists from the University of Osaka, discovered that in low-oxygen areas near colon tumors, normally supportive fibroblasts—cells that preserve tissue structure—transform into inflammatory fibroblasts that facilitate cancer growth. These transformed cells release growth-promoting factors such as epiregulin, and also produce Wnt5a, a protein that inhibits the formation of new blood vessels in their surroundings. This process helps maintain the hypoxic environment, which supports the survival of these inflammatory fibroblasts and, indirectly, the tumor itself.

The research team validated these findings by analyzing human samples from patients with healthy colons, inflammatory bowel disease, and colon cancer, alongside mouse model data. They observed that the transformation of fibroblasts and the secretion of Wnt5a are common in both human and animal models, suggesting a fundamental role in tumor development.

This insight opens new avenues for targeted therapies. Instead of just attacking cancer cells directly, future treatments could focus on blocking Wnt5a-producing fibroblasts, positioning them as a third key target alongside immune and cancer cells. Such strategies could be particularly impactful for colon cancer, which remains a leading cancer type in Japan, and for other inflammatory diseases like inflammatory bowel disease.

Understanding how hypoxia fosters a tumor-promoting environment challenges previous assumptions and highlights the importance of the tumor microenvironment in cancer progression. This research underscores the complexity of tumor biology and points towards innovative therapeutic strategies that could alter the course of colon cancer treatment.

Source: https://medicalxpress.com/news/2025-05-oxygen-deficiency-tumors-indirectly-colon.html