NORMAL CELL COMPETITION — HEALTHY CELLS ELIMINATING unhealthy cells — may be an important reason cancer relapses occur months or years after a patient believes there are free of cancer. Today, we look at a new theory about why cancer spreads or metastasizes.
A recently published mouse study from the University of Texas Southwestern (USA) illustrates that cell competition, a normal process, could contribute to cancer recurrences.
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When Breath Becomes Air
The diagnosis was immediate: Masses matting the lungs and deforming the spine. Cancer. In my neurosurgical training, I reviewed hundreds of scans for fellow doctors to see if surgery offered any hope. I’d scribble in the chart, ‘Widely metastatic disease — no role for surgery,’ and move on. But this scan was different: It was my own. — Paul Kalanithi
What is metastasis?
Metastasis or cancer spread to distant sites, is not uncommon for most cancers. For example, a surgeon may remove primary kidney cancer. Months to years later, one may find the spread of cancer to distant organs such as the lungs.
Circulating tumor cells can acquire the ability to penetrate the walls of lymph or blood vessels. The tumor cells can then circulate throughout the bloodstream to other body sites.
Circulating Tumor Cells: a window into cancer biology and metastasis
When cancer spreads through the lymphatic system, it is known as lymphatic spread. On the other hand, cancer spread through the bloodstream is known as hematogenous spread. Once these tumor cells arrive at a distant organ, they can re-penetrate the vessel wall and multiply. A new tumor forms at a distant site.
Once the tumor cells metastasize, we call the new tumor a secondary (or metastatic) tumor. Because the cells appear similar to those in the original (primary) tumor, we call the tumor in the lung metastatic breast cancer if the original site was the breast. The chances for cure significantly drop when metastases are present.
Metastasis — A new theory of cancer spread
Cell competition is a normal process in which healthy tissues eliminate unhealthy cells.
The researchers discovered that cell competition within the primary tumor causes the displacement of less-fit cells into the bloodstream. Unfortunately, not all of the displaced cells die. Some maintain the ability to survive in the bloodstream and set up shop in distant organs such as the lungs, liver, bone, and other structures.
The researchers created a mouse model of metastases by implanting human kidney cancer (renal cell carcinoma, or RCC) that carried extra genes to make the cells glow and resist a particular antibiotic.
Four weeks later, the scientists cut out the primary tumors that grew at the implantation site and monitored for metastasis by looking for glowing cells. While bioluminescent imaging showed no metastases over the next five months, the researchers discovered cancer cells in the lungs that glowed and resisted the antibiotic.
After the researchers grew these metastatic cancer cells with primary cancer cells in Petri dishes, they discovered that the primary tumor cells took over the mixture; more primary cancer cells survived. In other words, the metastatic cells lose the competition with the primary tumor cells. But, when the scientists implanted the metastatic cells in mice, the animals grew tumors.
The dominant, aggressive cancer clone does not necessarily drive disease progression; a non-dominant less-fit clone may drive spread from the primary tumor.
An additional study showed that the SPARC gene plays a key role in cancer cell displacement and establishment in distant organs. When SPARC activity decreased in the primary tumor, there appeared to be less displacement of cancer cells; depletion of SPARC in cancer cells that had spread to the lungs led to a higher metastatic tumor burden.
SPARC: a matricellular regulator of tumorigenesis
Could we profile primary tumor genes to understand metastasis risk better? We could then modify our follow-up recommendation. Might we target selected genes to prevent the cancer cells from leaving the primary tumor?
Thank you for joining me in this new theory about why cancer spreads. I hope you have a joy-filled day. Oh, one more thing: Please consider signing up to follow this blog. Thank you.
The information I provided in this blog is for educational purposes only and does not substitute for professional medical advice. Please consult a medical professional or healthcare provider if you seek medical advice, diagnoses, or treatment. I am not liable for risks or issues associated with using or acting upon the information in this blog.
