Key to Spread of Breast Cancer Identified in New Study

Breast Cancer in the News
A key player in the spread of breast cancer has been identified by researchers at Albert Einstein College of Medicine of Yeshiva University. Indeed, as a woman currently in treatment for triple-negative breast cancer, it is not cancer in my breast that I fear most, but the spread of that breast cancer to other areas of my body.

Learning how breast cancer spreads beyond the primary tumor is crucial in finding methods of treating breast cancer in the early stages, before it becomes metastatic disease.

“By focusing on sites where cancer had spread, we were able to detect a molecule that stimulates metastasis. This raises the possibility that metastasis could be kept from progressing — or even prevented — if the stimulating molecule could be blocked. This we achieved in mouse models of breast cancer,” said the study’s lead author, Jeffrey Pollard, Ph.D., professor of developmental and molecular biology and of obstetrics & gynecology and women’s health at Einstein.

What is metastasis? Metastasis starts when cells break away from the primary tumor and obtain the ability to move on their own. Invading nearby blood vessels, they are then carried by the bloodstream to other parts of the body. These tumor cells escape from vessels in a process known as extravasation. Once these tumor cells break free from blood vessels, they create new — and deadly — tumors in distant locations.

Dr. Pollard’s earlier research revealed that macrophages — immune system cells whose functions include fighting infections — actually promote the spread of cancer. Macrophages not only assist tumor cells during both intravasation and extravasation, but also help those cells take root in their new locations and grow into metastatic tumors. The new study investigated the process by which these macrophages are recruited to metastatic sites and subsequently promote tumor-cell extravasation, seeding, and tumor growth.

“These findings have potential implications for therapy, since in human breast cancer we know that CCL2 expression and macrophage infiltration are associated with poor prognosis and metastatic disease. If we can develop ways to inhibit these processes, we might be able to slow or stop breast cancer from spreading,” said Dr. Pollard.

Details from the study findings:

Using models of human and mouse breast cancer, the researchers demonstrated that when breast tumor cells travel to the lung, these cells secrete CCL2, a chemokine molecule (i.e., one that attracts cells). CCL2 attracts immune cells called inflammatory monocytes — in particular, those bearing receptors for CCL2, which then develop into macrophages. The monocytes and macrophages “invited” by CCL2 signaling then facilitate extravasation – the critical step in metastasis in which bloodborne tumor cells cross the vessel wall and implant in nearby tissue. One way monocytes help tumor cells escape from blood vessels and cause metastasis, the Einstein researchers found, is by secreting vascular endothelial growth factor, or VEGF, a substance that makes blood vessels leaky at the site where tumor cells exit from them.

Once the tumor cells are seeded, inflammatory monocytes continue to flock to the metastatic site – now attracted by CCL2 secreted not only by the tumor cells but also by nearby lung tissue that the tumor cells have targeted. In turn, these continuously recruited monocytes and the resultant macrophages promote the growth of the emerging metastatic tumor.

To confirm their findings, the researchers used anti-CCL2 antibodies to suppress CCL2 signaling in a mouse model of human metastasis – with striking results. In lungs challenged with metastatic tumor cells, the anti-CCL2 antibodies inhibited the influx of inflammatory monocotyes and macrophages to the metastatic sites, and the number of metastatic sites that developed in the lungs was markedly reduced. In addition, the mice lived much longer when CCL2 signaling was blocked.

The research was funded by grants from the National Cancer Institute of the National Institutes of Health. The findings are published in journal Nature.

Sources: Albert Einstein College of Medicine of Yeshiva University“Einstein Scientists Find Crucial Molecule Involved in Spread of Breast Cancer”; Bin-Zhi Qian, Jiufeng Li, Hui Zhang, Takanori Kitamura, Jinghang Zhang, Liam R. Campion, Elizabeth A. Kaiser, Linda A. Snyder, Jeffrey W. Pollard – CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature, 2011; DOI: 10.1038/nature10138; “Crucial molecule involved in spread of breast cancer identified; Findings suggest strategy for halting metastasis.” ScienceDaily, 8 Jun. 2011. Web. 8 Jun. 2011; Einstein

Breast Cancer in the News
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Coming Soon: Breast Cancer Survivor Profiles
If you’re a triple-negative breast cancer survivor and you’d like to share your story, email

Living with Triple-Negative Breast Cancer Series
#1 The Lump in my Breast: Meeting the Enemy
#2 Most Breast Lumps are Non-Cancerous: Would mine be?
#3 The Mammogram, the Ultrasound, and ‘the Look’
#4 The Biopsy and Breast Cancer Confirmation
#5 A New Twist: It’s Triple-Negative Breast Cancer
#6 Before the Mastectomy: Planning for the Future
#7 Mastectomy Day: What it’s like to lose a breast
#8 After the Mastectomy: Unveiling and Staging
#9 10 Odd Things to Say to Someone with Breast Cancer
#10 Cancer Battle Plan Phase 2: Chemotherapy
#11 5 Things I Love About my Very Expensive Health Insurance
#12 10 Simple Gestures of Kindness with Healing Power
#13 Half a Year on Chemotherapy and Taking Nothing for Granted
#14 Breast Cancer Treatment: Weighing Reward and Risk

Take Action! Sign the petition: We can end breast cancer by 2020

Author’s Note: This is article is part of a series chronicling my first-hand patient perspective of life with Triple-Negative Breast Cancer. Without being overly self-indulgent, I hope to convey the raw emotion that comes with such a diagnosis… and the process of living with and beyond it. Entries will appear in Care2 Causes and in Care2 Healthy & Green Living. Follow on Twitter @AnnPietrangelo




Vlasta Molak
Vlasta M6 years ago

China epidemiological study clearly indicates that it is the FOOD! Japanse and Chinese women who used to eat mostly vegetable based diets had 5-10 TIMES less incidence and prevalence of breast cancer. So reduce your intake of meat and milk products and you will drastically reduce your chances of not only breast cancer but your heart disease, other cancers, blood pressure diabetes etc. all correlated with rich US diet!

Dave G.
Dave G6 years ago

@Martha E. - You could be onto something. We KNOW that corporate agriculture has been playing fast and loose with growth hormones, antibiotics and genetic engineering. We also know that certain toxins can be stored/accumulate in body fat.
I wouldn't be surprised at all to learn that there IS a connection!

Martha Eberle
Martha Eberle6 years ago

Important information, but I am interested in why American women get so much breast cancer. I've really always thought it must be related to our diet and how that affects the parts of the body with body fat, like breasts. The incidence of breast cancer has increased so dramatically in our supposedly advanced country, that I've tried to come up with a common sense reason why.

Pat Vee
Pat Vee6 years ago

Any advance in the understanding of this disease must be a plus.

Dana W.
Dana W6 years ago

Thanks for the info.

Emily F.
Emily F.6 years ago

It's a shame that Care2 endorses mouse studies of breast cancer since these are not relevant to humans. There are numerous differences between rodent biology, physiology and pathology that make them - and other animals - poor models of human cancer. Just two of these: Rodents have a maximum life span of three years and metabolize substances much more quickly than humans; for example, they metabolize drugs in 3 hours. Rodents are purposely bred for various genetic traits and are often predisposed to develop tumors. Stressors in the lab that have been found to affect physiology include handling, lights, bedding material, caging, cage mates, and food. I write extensively about the differences between humans and animals in toxicology testing in my book, Lethal Laws: Animal Testing, Human Health and Environmental Policy (1997, Zed/St Martin's Press). In vitro studies with human cells and epidemiological studies will tell us what we need to know about HUMAN cancer, not studies on mice. Animal testing is also part of a life-destroying paradigm that followers of Care2 - and Care2 itself as an organization - should reject. We have sent people to outer space and developed countless sophisticated medical and other technologies. Animal research is a relic of an unenlightened past that we can, and must, leave behind if we are to advance as a society and find cures to the many human diseases that still plague us despite hundreds of years of research on animals.

Dave Tohunga
Dave te tohunga6 years ago

recommend watching the 'Burzynski movie' online (google it)

Anja N.
Justin R6 years ago

Thanks again Ann.

Sound Mind
Ronald E6 years ago


Dave G.
Dave G6 years ago

Cautiously optimistic - but Extremely Mistrustful of Big Pharma!