What Makes a Colon Cancer Cell Dangerous Is Where It Lives

Even after multiple rounds of chemotherapy, cancer patients can relapse. Whether they relapse or not depends on the activity of cells in their tumors: if the harmful cells act up and multiply, the cancer returns. Relapse is especially prevalent in colon cancer, affecting nearly half of all patients.

A new study in Nature Cell Biology by NYSCF – Robertson Stem Cell Investigator and Professor of Molecular Oncology at the Academic Medical Center in Amsterdam Louis Vermeulen, MD, PhD, examines the behavior of tumor-forming cells in colon cancer and finds that a big player in what makes a cell malignant is its location within a tumor.

The team studied the development of human tumor cells implanted into mice, looking specifically at cells called cancer stem cells, which drive the development of tumors and help them metastasize (spread to other locations in the body). As the tumors developed, the researchers noticed that the malignant cancer stem cells were the ones located on the tumor’s edge.

Their findings suggest that more than anything, what prompts a cell to turn dangerous and spark a relapse is its environment – or as it’s called for a cell, its microenvironment. Even cells that do not express cancer stem cell markers are likely to start taking on the damaging properties of cancer stem cells once they reach the outskirts of a tumor.

The team believes that the cells in this particular microenvironment may become problematic because they are located near cells called cancer-associated fibroblasts (which encourage blood vessels to grow around a tumor and keep it active). The researchers also identified a protein called osteopontin that is produced by cancer-associated fibroblasts and promotes growth of the harmful cancer stem cells. Osteopontin could therefore serve as a potential therapeutic target.

In addition to the detection of osteopontin, the realization that spatiotemporal dynamics play a big role in colon cancer recurrence will help scientists create more effective therapies. Current treatments often attempt to simply attack cancer stem cells across the board, but this study shows that these treatments will not suffice to prevent a relapse. We have to also keep in mind that cells that do not behave like cancer stem cells can become malignant once they move to the edge of the tumor, and that this process should also be addressed in future treatments.