Thursday, March 26, 2015

Breast Cancer Metastasis and the Weapons Against It

Everyone knows that cancer is bad, and that's a given.  But how does a cancer such as breast cancer come to be so dangerous to the human body when it can be so easily removed? The answer is metastasis; when the cancerous cells remove themselves from the primary tumor and spread to the other parts of the body.  While this seems simple in concept, breast cancer must go through many steps before it is conditioned to the microenvironment that is found in the bone.

Primary tumors are known to associate with mesenchymal cells, which cross-communicate to produce tumors that are more suited to the local tumor environment.  These tumors are selected over cells that are less suited, and so tumors with these receptors become overly selected for and start to dominate the primary tumor tissue.  By being selected, these tumors become more sensitive to a chemokine in the bloodstream that makes them more resistant to activated cell death and makes them more mobile. This chemokine, CXCL12, is released by bone in order to recruit immune cells to inhibit inflammation based bone destruction.  However, once breast cancer cells have been attuned to this chemokine with an increase in the receptors, CXCR4/7, they are also prepared to survive and proliferate once they reach the source of the chemokine.

Once these cancer cells reach the bone marrow, they are not only suited to this environment, but primed to strive in it.  Since they are in an environment with high CXCL12, they proliferate more than in the primary tumor, as well as causing more angiogenesis to the secondary tumor site and increasing inflammation, causing a positive feedback loop.

What steps have been taken to stop this process, you ask? Well, there have been recent trials that test the effectiveness of a CXCR4 blocker in order to lower the tumor's sensitivity to CXCL12 and limit its metastasis to bone.  This drug, originally used to block HIV entry to immune cells, blocks all cells' receptors to CXCL12.  While this may weaken the immune response to bone destruction, it has a much lower toxicity level than many other FDA approved cancer drugs that kill rapidly dividing cells indiscriminately.  This relatively safe method is still being tested with favorable results and may bring light on a new way to treat patients.


  1. I've always been curious as to the exact mechanism for which cancer spreads through the blood stream. Principally, the vascular system is used for transport, but how exactly does cancer spread through it? The most obvious answer to me would be that cancerous cells travel through the blood stream, but I'm not sure. I wasn't aware that other types of cells beside blood cells traveled through blood.
    -Patrick O'Loughlin

  2. Great blog! You mentioned that mesenchymal cells cross-communicate to produce tumors. I was just curious if this involved some sort of mutation or do mesenchymal cells just naturally produce tumors? I just thought most tumors were created through mutation of tumor suppressor proteins/genes.

    -Amanda Okpoebo

  3. So this treatment is used for bone metastasis only? Are there similar solutions for metastasis to other tissues?
    -Meghan Harrington

  4. As someone that has interest in pursuing a career in oncology this was a very interesting read. If cancer is something that interests you, or anyone else reading this, i would HIGHLY recommend reading the book "The Emperor of Maladies" by Siddhartha Mukherjee. The author, an oncologist, describes the work as a "biography" of the disease. It's filled with really interesting information about the history of the disease and the battle against it as well as a number of personal anecdotes that are very heart-felt. One of the more interesting stories is about Atossa, who was the queen of Persia around 500 BC. Atossa developed breast cancer but would wrap herself in sheets to hide her condition. She refused treatment until finally a Greek slave convinced her to allow him to remove the tumor in her breast. The operation was a success, and soon afterwards the Greek slave, wanting to be closer to home, persuaded Atossa to shift her campaign westward and invade Greece. This decision led to 50 years of war between the two empires. In a sense, Atossa's breast cancer helped to shape the history of Europe!

  5. I enjoyed the pictures, they added a great visual aspect. I was just wondering what kind of implications this treatment has on the patient's immune response in particular. You mention that the response to bone destruction is weakened, but are any other pathways affected as well?

    -Carolyn McDonagh