Rethinking Metastasis and Early-Stage Tumors

March 11, 2024

Scientists at The Scripps Research Institute (TSRI) have discovered why some cancers may reoccur after years in remission.

The findings, published recently in the journal Cell Reports, show that invasive tumors can begin sending out tumor cells far earlier than previously thought.  These escaping cells, which can enter the bloodstream before the primary tumor is detected, may seed secondary tumors that don’t show up for years.

The scientists also discovered that the escaping tumor cells reach the bloodstream by entering blood vessels deep within the dense tumor core, overturning the belief that metastatic cells come from a tumor’s invasive borders.

For the study researchers used cancer cell lines generated from human fibrosarcoma and carcinoma tumors and found that primary tumors can send out cells early on, independent of cancer invasion into adjacent tissue, possibly explaining why doctors often see secondary tumors appearing earlier than they would have predicted.  This finding may also shed light on why patients with early stage tumors still have a risk of developing metastatic disease.  The metastases may have been seeded when the primary tumor was even too small to be visualized.

The study is also the first to examine entire tumors to find out exactly where escaping cells come from. The scientists tagged tumor cells with a florescent protein and used high-resolution microscopy techniques to map blood vessels across entire tumors, from the tumors’ dense cores to their invasive tendrils.  This approach gave the researchers a way to finally analyze the escape process and were surprised to find that the vast majority of tumor cells entered blood vessels within the tumor core, not in the invasive tendrils.

These outcomes could be extremely important for cancer patients.  The research suggests a primary tumor does not have to be highly invasive to seed metastases.  In fact, doctors may want to reconsider the time frame for the onset of cancer cell dissemination.

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