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Experimental agent reduces breast cancer metastasis to bone
November 04, 2009Researchers have reduced breast cancer metastasis to bone using an experimental agent to inhibit ROCK, a protein that was found to be over-expressed in metastatic breast cancer. In a study in mice, the team of researchers from Tufts University School of Medicine, the Sackler School of Graduate Biomedical Sciences at Tufts, and Tufts Medical Center report that inhibiting ROCK, or Rho-associated kinase, in the earliest stages of breast cancer decreased metastatic tumor mass in bone by 77 percent and overall frequency of metastasis by 36 percent. The results suggest that ROCK may be a target for new drug therapies to reduce breast cancer metastasis.
"While the primary tumor causes significant illness and requires treatment, metastasis accounts for over 90 percent of breast cancer-related deaths. There are no treatments to eradicate metastasis. Establishing ROCK's role in the spread of breast cancer and identifying agents to inhibit ROCK brings us one step closer to an approach that might reduce metastasis in the future," said senior author Michael Rosenblatt, MD, professor of physiology and medicine at Tufts University School of Medicine and member of the cellular and molecular physiology program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts. Rosenblatt is also dean of Tufts University School of Medicine.
"We also found that using shRNA - short hairpin RNA - to knock down ROCK expression slowed metastasis. In order for cancer cells to migrate, an extensive transportation apparatus is required. ROCK directs the formation of this apparatus, but use of the ROCK inhibitor as well as shRNA rendered the cells' transportation mechanism ineffective, significantly reducing breast cancer metastasis to bone," said first author Sijin Liu, PhD, research instructor and member of the Rosenblatt Laboratory at Tufts.
"This study also revealed that a specific microRNA cluster, 17 through 92, is associated with ROCK expression and breast cancer metastasis. The microRNA cluster responded to ROCK inhibition, which provides insight into the mechanism driving metastasis and is a finding that will be of particular interest to researchers focused on the role of microRNAs in gene expression," continued Liu.
Rosenblatt, Liu, and colleagues used luminescent imaging to observe ROCK's effect on breast cancer metastasis. The researchers found that inserting high levels of ROCK in non-metastatic cancer cells caused the cells to metastasize to several secondary sites, while cells with no ROCK exposure remained localized. The researchers then used an experimental agent (Y27632) or shRNA to reduce ROCK activity in seven mice with metastatic tumors, finding a significant decrease in metastasis to bone compared to six untreated mice.
Breast cancer is the second leading fatal cancer in women, and affects just under one in eight women in the United States. Bone is the most common site of breast cancer metastasis, affected three times more often than the lungs or liver.
Tufts University, Health Sciences
"This study also revealed that a specific microRNA cluster, 17 through 92, is associated with ROCK expression and breast cancer metastasis. The microRNA cluster responded to ROCK inhibition, which provides insight into the mechanism driving metastasis and is a finding that will be of particular interest to researchers focused on the role of microRNAs in gene expression," continued Liu.
Rosenblatt, Liu, and colleagues used luminescent imaging to observe ROCK's effect on breast cancer metastasis. The researchers found that inserting high levels of ROCK in non-metastatic cancer cells caused the cells to metastasize to several secondary sites, while cells with no ROCK exposure remained localized. The researchers then used an experimental agent (Y27632) or shRNA to reduce ROCK activity in seven mice with metastatic tumors, finding a significant decrease in metastasis to bone compared to six untreated mice.
Breast cancer is the second leading fatal cancer in women, and affects just under one in eight women in the United States. Bone is the most common site of breast cancer metastasis, affected three times more often than the lungs or liver.
Tufts University, Health Sciences
Breast Cancer Metastasis Current Events and Breast Cancer Metastasis News RSSMicroRNA-mediated metastasis suppression
Metastases are responsible for over 90% of cancer deaths. In the upcoming issue of G&D, Dr. Robert Weinberg (MIT) and colleagues lend molecular insight into how microRNAs suppress tumor metastasis.
Newly appreciated membrane estrogen receptor important therapeutic target for breast cancer
New research at Rhode Island Hospital has uncovered the biological effects of a novel membrane estrogen receptor, a finding that has potential implications for hormonal therapy for breast cancer.
Genes found to play a role in breast cancer's spread to the brain
New research led by investigators at Memorial Sloan-Kettering Cancer Center (MSKCC) identifies three genes that specifically mediate the metastasis, or spread, of breast cancer to the brain and illuminates the mechanisms by which this spread occurs. The study was published online today in Nature.
New Test May Predict Breast Cancer Metastasis
Researchers at NewYork-Presbyterian Hospital/Weill Cornell Medical Center have identified a new marker for breast cancer metastasis called TMEM, for Tumor Microenvironment of Metastasis.
NYU Langone Medical Center researchers find micro RNA plays a key role in melanoma metastasis
Scientists have long wondered how melanoma cells travel from primary tumors on the surface of the skin to the brain, liver and lungs, where they become more aggressive, resistant to therapy, and deadly.
Interactive gene 'networks' may predict if leukemia is aggressive or slow-growing
Rather than testing for individual marker genes or proteins, researchers at the University of California, San Diego (UC San Diego) and the Moores UCSD Cancer Center have evidence that groups, or networks, of interactive genes may be more reliable in determining the likelihood that a form of leukemia is fast-moving or slow-growing.
Small RNAs can prevent spread of breast cancer
Howard Hughes Medical Institute researchers have identified small pieces of ribonucleic acid (RNA) that suppress the spread of breast cancer to the lungs and bone. The new research shows that the most invasive and aggressive human breast cancer tumors are missing three critical microRNA molecules.
Molecules can block breast cancer's ability to spread
Researchers have identified a specific group of microRNA molecules that are responsible for controlling genes that cause breast cancer metastasis.
UC San Diego researchers improve accuracy of breast cancer prognoses
One of the many unknowns facing women who are diagnosed with breast cancer is predicting the likelihood that the cancer will spread to other parts of the body - metastasize.
Dietary calcium could possibly prevent the spread of breast cancer to bone
A strong skeleton is less likely to be penetrated by metastasizing cancer cells, so a fortified glass of milk might be the way to block cancer's spread.
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Breast cancer metastasis to the gasserian ganglion.(Letters to the Editor): An article from: Southern Medical Journal by Federico L. Ampil (Author), Gary V. Burton (Author), Mardjohan Hardjasudarma (Author), Travis Henley (Author) This digital document is an article from Southern Medical Journal, published by Thomson Gale on January 1, 2006. The length of the article is 762 words. The page length shown above is based on a typical 300-word page. The article is delivered in HTML format and is available in your Amazon.com Digital Locker immediately after purchase. You can view it with any web browser. Citation Details Title: Breast cancer metastasis to the gasserian ganglion.(Letters to the Editor) Author: Federico L. Ampil Publication: Southern Medical Journal (Magazine/Journal) Date: January 1, 2006 Publisher: Thomson Gale Volume: 99 Issue: 1 Page: 93(2) Distributed by Thomson... | |
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Advanced Breast Cancer: A Guide to Living with Metastatic Disease, 2nd Edition (Patient-Centered Guides) by Musa Mayer (Author) Newly updated and revised, this is the only book on breast cancer that deals honestly with the realities of living with metastatic disease, yet offers hope and comfort. It features the stories of 40 women and men as they struggle to come to terms with metastatic breast cancer. All aspects of facing advanced breast cancer are covered, including: coping with the shock of recurrence, seeking information and making treatment decisions, communicating effectively with medical personnel, finding support, and handling disease progression and end-of-life issues. Most people assume the recurrence of breast cancer means an immediate death sentence. The eloquent voices in Advanced Breast Cancer speak of a different reality: that women with metastatic breast cancer generally go on to live... |
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Atlas of Selective Sentinel Lymphadenectomy for Melanoma, Breast Cancer and Colon Cancer (Cancer Treatment and Research) by Stanley P.L. Leong (Editor) Atlas of Selective Lymphadenectomy for Melanoma, Breast Cancer and Colon Cancer emphasizes a multidisciplinary approach combining the experiences of a nuclear medicine physician, surgeon, and pathologist. This is an important reference also for researchers and clinicians who want to become familiar with sentinel lymph node mapping. The underlying thesis in solid tumor biology is that metastasis in general starts in an orderly progression with lymphatic spread first to the sentinel lymph node (SLN) in the nearest lymph node basin. Therefore, the logical approach is to harvest that specific SLN for thorough analysis. |
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