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Blood Cells That Clot Wounds May Help Breast Cancer Spread
Mouse studies reveal a feedback loop: Platelets help breast cancer start, then cancer leads to platelets that support metastasis.
The Challenge
The tiny blood cells that help the body heal wounds, called platelets, float along in the bloodstream until they are activated by a bleeding wound or injury. Then, they multiply, go to the place that’s bleeding, adhere to other platelets and damaged blood vessels, and release proteins to form blood clots that “plug” the damaged part of a blood vessel.
But, if platelets are “inappropriately” activated, they may contribute to the growth and spread of cancer through the process of metastasis. Researchers have already discovered a lot about the relationship between platelets and tumors. For instance, an abnormally high platelet count may:
- Increase the risk of developing certain cancers, including colon, lung, ovarian, and stomach.
- Be a sign of an undetected cancer.
- Indicate that cancer is more likely to spread to other parts of the body if the count is high at the time of diagnosis.
- Reduce the chance of surviving cancer.
Platelets may be involved in many processes of tumor development. For instance, they may help tumor cells survive and reproduce, escape detection by the immune system, and penetrate capillaries (or help new ones grow) to spread through the bloodstream and set up a new tumor far from the original one (distant metastases).
Featured Term:
Platelets
Also known as thrombocytes, platelets are small blood cells with the primary role of preventing or stopping bleeding in the body. Platelets have also been found to have a role in the development and spread of certain types of cancer.
Until now, though, research hasn’t focused as much on the opposite relationship—how cancerous tumors affect platelets. A few studies have looked at the interactions between some types of cancer and platelets. But little has been discovered about how breast cancer affects the production of platelets, specifically how it affects the largest cells in bone marrow—megakaryocytes—that make platelets.
The Research
In her lab, American Cancer Society (ACS)-funded researcher Elisabeth Battinelli, MD, PhD, studies the connection between platelets and the spread of cancer. In a study recently published in Science Advances, she and colleagues examined mice with breast cancer to better understand why and how cancer affects the growth and activity of platelets.
The team found that the mice with breast cancer in their lab did not have an increased number of platelets (like women with breast cancer do). However, the platelets the mice had were very large. The researchers also found evidence suggesting that these platelets were not normal. In fact, they looked similar to the platelets sometimes seen in people with cancer.
Our study is the first to show how the presence of breast cancer leads to changes in megakaryocytes, the cellular factories in the bone marrow that manufacture platelets. The altered megakaryocytes produce platelets with changes in quality that may make it easier for cancer to spread.”
Elisabeth Battinelli, MD, PhD
Brigham and Women’s Hospital in Boston
ACS Research Grantee
Battinelli and her team discovered that cancer cells send out signals that have a direct effect on megakaryocytes in the bone marrow, changing how these cells look and behave. Specifically, the megakaryocytes:
- Are smaller and fewer in number
- Have abnormal numbers of chromosomes
- Make more pro-inflammatory proteins, which are associated with the progression of tumors
Platelets made by these altered megakaryocytes also had higher levels of pro-inflammatory proteins. This not only suggests that the megakaryocytes passed on the tumor-induced changes to platelets they produced, but also that those changes contribute to platelets’ support of metastasis.
Why It Matters
This study reports for the first time that breast cancer alters megakaryocytes and shows how cancer-associated changes in these platelet precursors promote metastasis.
The investigators expect that by learning more about how cancer cells and other cells send signals to each other, they can find ways to disrupt the cancer-promoting crosstalk.
These discoveries could lead to new biomarkers to guide precision oncology care and improve treatments for breast cancer.
The study authors conclude, “Despite the findings presented in this study, it remains largely undetermined which tumor-derived factors affect megakaryopoiesis (the maturation of megakaryocytes so that they produce platelets) during breast cancer progression.” Future studies, they say, should determine whether cancer directly affects megakaryocytes via signals sent from the tumor or by increasing inflammatory responses.
