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.
“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
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Coming Soon: Breast Cancer Survivor Profiles
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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
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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