a new wrinkle on bc stem cells--and an already approved metastasis preventing drug?

[Lani]

from the BBC:
Stem cells 'prompt cancer spread'

Stem cells may allow breast cancer cells to spread
Dangerous changes in cancer cells which allow them to spread around the body could be triggered by the body's own stem cells, say US scientists.
A Whitehead Institute team found human breast cancers in mice are more likely to spread if mixed with stem cells from the bone marrow.

They believe these changes could be blocked or reversed - making the cancer less deadly.

UK experts said the Nature study could point to future treatments.


It's becoming increasingly clear that many cancers aren't just made up of cancer cells, but they are rogue tissues that also contain many other types of cells

When an original cancer spreads to form new tumours in other parts of the body such as the lung or liver, this is called metastasis, and often means that the patient is far less likely to be cured of the disease.

Doctors hope that by understanding how and why a tumour suddenly changes its behaviour, a treatment could be found to stop this happening, and keep the cancer fixed in one part of the body.

The latest research has linked the arrival of a particular type of "stem cell" to metatasis in breast cancer cells.

Mesenchymal stem cells are found in the bone marrow, and are a "master cell" used by the body to help generate new bone, fat, cartilage and muscle.

They were already a suspect in cancer spread after it was noticed that they naturally migrate in large numbers to tumour sites.

When the scientists mixed human breast cancer tumours in mice with these cells, there was seven times more cancer spread to the lungs compared with breast cancer tumours left to their own devices.

They are suggesting that the presence of the stem cells produces genetic changes in the cancer cells that make them metastasise - but once the cells spread, they change back to their original genetic state.

This, the researchers say, not only makes these key genes hard to spot, but means that dangerous changes in cancer cells are potentially reversible.

HIV treatment hope

The research has also highlighted a potential treatment to block the changes.

A chemical called cytokine CCL5, produced by the stem cells, had an effect on breast cancer cells in the laboratory.

Medication that blocks the action of this is already used to help patients with HIV - and they suggested it should be tried on patients with spreading cancer.

Dr Kat Arney, from Cancer Research UK, said: "It's becoming increasingly clear that many cancers aren't just made up of cancer cells, but they are rogue tissues that also contain many other types of cells.

"This is a very interesting paper, showing that mesenchymal stem cells may play a part in helping breast cancer to spread.

"Although these results don't tell us if exactly the same situation is present in cancers within humans - as they have been done using mice - it's a good indicator that these stem cells may play a role in breast cancer, and could point towards targets for future treatments."

[madubois63]

It may be too early in the morning for me, but I am not quite following this. Does this mean that any rouge breast cancer cells that may be floating in my body may have been "fixed" by the stem cell transplant? I understand this is all hypothetically thinking at this point, but...very interesting thoughts to say the least.

I was originally told that no transplant hospital wanted to treat me because of the breast cancer. The big fear is/was that the transplant could kick start the BC again. Many, many tests had to be done before the transplant was approved. Thank God the BC was NED then and that I continue to be. Maybe the mindset will change making it easier for people to get necessary treatments. Thoughts??? Thanks...

[Lani]

requisite mental alertness to evaluate whether or not the evidence presented(which requires reading the original paper) really moves me away from the stem cell theory of breast cancer as I now believe it, with stem cell or early progenitor cells lying dormant in the bone marrow for reactivation after receiving a "sleeping beauty kiss" from ? angiogenic factors or the correct immune environment or other stromal factors.

It all seemed rather complicated (which cancer can certainly be!) and convoluted and perhaps could be explained in alternative ways...but that was just my first impression. Am still on the road and exhausted. Will reevaluate this, but my impression also was...maybe, but you'll certainly have to prove it to me as I am doubtful. Just my first take on it...

[hutchibk]

How do we gain access to the HIV medication I wonder?

[Lani]

someone must start a trial using that drug for the offlabel purpose showing it is both effective and without unexpected side effects before they will consider giving to breast cancer patients.

[Cathya]

I found this article which might assist in clarifying the original....aka it seems a more straightforward explanation to me....lol.

Cancer cells enlist adult stem cells to promote metastasis

Alyssa Kneller , Whitehead Institute
October 31, 2007

Everyone knows that tumors are packed with cancer cells, but many normal cells live among these deviants. The normal cells form a structural framework called the stroma, which was once thought to resemble passive scaffolding. But a growing body of research suggests that cancer cells actively recruit normal cells from local and distant sites to the scaffolding, where they release signals that help the tumor thrive.
Beginning in 1999, several labs increased primary tumor growth by mixing fibroblasts (cells that contribute to the formation of connective tissue and the stroma of tumors) with cancer cells. This was the first proof that stromal fibroblasts actively foster the growth of cancer cells. Stated differently, cancer cells can co-opt normal cells to serve their own insidious purposes.
"This study provides the first direct evidence that a cancer cell's metastatic powers are not necessarily intrinsic to the cell itself," says Whitehead Institute member Robert Weinberg. "Rather, they might be influenced by the signals the cancer cell experiences from stromal cells in the context of the primary tumor."
Working with a different type of normal stromal cell, Weinberg's lab has now managed to facilitate metastasis--the spread of cancer cells from the primary tumor to distant sites. Postdoctoral researcher Antoine Karnoub has compelling evidence that some breast cancer cells recruit normal adult stem cells from bone marrow and force them to secrete a protein that fosters cancer cell movement and invasion. His results appeared online in Nature on Oct. 4.
"This study provides the first direct evidence that a cancer cell's metastatic powers are not necessarily intrinsic to the cell itself," says Weinberg, who is also an MIT professor of biology. "Rather, they might be influenced by the signals the cancer cell experiences from stromal cells in the context of the primary tumor."
The conscripts that confer these metastatic powers are mesenchymal stem cells (MSCs), which ordinarily generate bone, muscle, cartilage and fat. MSCs also play a critical role in healing wounds. Skin your knee, for example, and your body sends an emergency signal that prompts MSCs to leave their home in the bone marrow and travel to the site of the trauma. Here they help to reduce inflammation, form scar tissue and seal the wound.
"Sites of tumor formation are much like open wounds," Karnoub explains. "MSCs might very well home to those sites to aid with the healing process. Once there, they may get entangled with the tumor cells and actually help them grow."
To investigate this idea, he combined MSCs from a human hip with human breast cancer cells, implanted the mixture into the backs of mice and studied the growth of the resulting "mixed" tumors. As a control, he implanted cancer cells without MSCs into mice. To Karnoub's disappointment, both group's tumors grew to the same size and at the same speed.
Probing further, he found that while the first group's tumors metastasized, the second group's, for the most part, did not. Karnoub repeated this experiment with several other lines of human breast cancer cells and found others that demonstrated similar properties.
How did these lines of cancer cells acquire the dangerous ability to invade distant tissues?
Karnoub next examined the proteins made by the cells. He discovered that MSCs ramp up their production of a key protein called CCL5 in the presence of cancer cells, churning out about 60 times the normal amount. CCL5 is known to affect cell movement, and its levels are elevated in the blood of patients with advanced breast cancer. Could the cancer cells be "educating" the MSCs, instructing them to make CCL5, thereby promoting metastasis?
Karnoub tested this hypothesis by coaxing weakly metastatic breast cancer cells to produce lots of CCL5 in the absence of MSCs. These cells acquired the ability to move and migrate to distant tissues, confirming CCL5's key role in MSC moderated metastasis.
Tissue samples from patients provide clinical relevance. Researchers at Brigham and Women's Hospital and Dana-Farber Cancer Institute examined CCL5 expression in tumor stroma taken from breast cancer patients with invasive and noninvasive forms of the disease. High CCL5 levels correlated with invasive tumors and poor prognosis.
"MSC recruitment and CCL5 production could be responsible for metastasis in a significant subset of breast cancer patients, which has implications for diagnosing and treating the disease," Karnoub asserts. "This protein sheds light on how breast cancers mine the body's own resources to progress."
It also offers a promising therapeutic target. Karnoub was able to halt metastatic spread in the mice with mixed tumors by simply blocking CCL5 signaling.
This research is funded by the Breast Cancer Research Foundation, the Ludwig Trust, the Susan G. Komen Breast Cancer Foundation, the Dana-Farber/Harvard Cancer Center Specialized Program of Research Excellence in Breast Cancer and the National Institutes of Health.

[Lani]

I did my homework, looking up HIV drugs which inhibit CCL5 and found: the FDA-approved CCL5-RANTES inhibitor recently approved for treatment of HIV is
maraviroc from Pfizer

[sarah]

Lani,
You always have such interesting and up to date information - it is so appreciated. Although sometimes I have a hard time understanding it!
Thanks and Happy New Year
sarah

[juanita]

I read the articles y'all post here and am so amzed at your knowledge. My question is where do you find these? Or find the time to find them? I have a hard enough time checking on here and reading everything. I do REALLY, REALLY appreciate all that all of you do post. I just wish I'd known about you when first diagnosed instead of later.