Breast squeezing reported to revert breast cancer cells
A new study has reported that squeezing the breast can revert and stop the out-of-control growth of breast cancer cells. The results of the study could lead to the development of new therapies to treat breast cancer that are not based on chemotherapy or radiation. Researchers affiliated with the UC Berkeley and the Lawrence Berkeley National Laboratory reported their findings on December 17 at the annual meeting of the American Society for Cell Biology in San Francisco.
Mechanical forces alone were found to revert breast cancer cells even though the genetic mutations responsible for malignancy remain; thus, producing a nature-versus-nurture battle in determining a cell’s fate. “We are showing that tissue organization is sensitive to mechanical inputs from the environment at the beginning stages of growth and development,” noted principal investigator Daniel Fletcher, professor of bioengineering at Berkeley and faculty scientist at the Berkeley Lab. He noted, “An early signal, in the form of compression, appears to get these malignant cells back on the right track.”
Breast tissue is known to change throughout a woman’s life in response to changes in her reproductive cycle: during the menstrual cycle, pregnancy, and lactation (milk production). For example, during lactation, acini (berry-shaped structures that secrete milk) are formed. These structures are the result of rotation of breast cells to form an organized structure. Growth of these cells ceases at an appropriate time. However, breast cancer cells grow continuously in a disorganized fashion. Furthermore, they do not rotate in an appropriate manner when forming acini.
The traditional view of cancer development focuses on genetic mutations within the cell. However, Mina Bissell, PhD, Distinguished Scientist at the Berkeley Lab, conducted pioneering experiments that showed that a malignant cell is not doomed to become a tumor; rather, its destiny is dependent on its interaction with the surrounding microenvironment. Her research found that manipulation of this environment, via the introduction of biochemical inhibitors, could revert mutated mammary cells to normal behavior. Dr. Fletcher collaborated
Collaboration between Dr. Fletcher and Dr. Bissell’s lab resulted in the development of a new concept: mechanical rather than chemical factors can influence cancer cell growth. Gautham Venugopalan, a PhD candidate in Dr. Fletcher’s lab, conducted the new experiments as part of his recently completed Ph.D. dissertation at UC Berkeley. He noted, “People have known for centuries that physical force can influence our bodies. When we lift weights, our muscles get bigger. The force of gravity is essential to keeping our bones strong. Here we show that physical force can play a role in the growth — and reversion — of cancer cells.”
The researchers grew malignant breast epithelial cells in a gelatin-like substance that had been injected into flexible silicone chambers. The flexible chambers allowed the researchers to apply a compressive force during the first stages of cell development. The investigators found that over time, the compressed malignant cells grew into more organized, healthy-looking acini that resembled normal structures, compared with malignant cells that were not compressed. Via time-lapse microscopy over several days, they showed that early compression also induced coherent rotation in the malignant cells, a characteristic feature of normal development. Of significance, those cells stopped growing once the breast tissue structure was formed, even though the compressive force had been removed. “Malignant cells have not completely forgotten how to be healthy; they just need the right cues to guide them back into a healthy growth pattern,” explained Venugopalan.
As part of the experiment, the investigators further added a drug that blocked E-cadherin, a protein that helps cells adhere to neighboring cells. When they did this, the malignant cells returned to their disorganized, cancerous appearance; thus, negating the effects of compression and demonstrating the importance of cell-to-cell communication in organized structure formation.
The researchers caution that they are not proposing the development of compression bras as a treatment for breast cancer. Dr. Fletcher said, “Compression, in and of itself, is not likely to be a therapy. But this does give us new clues to track down the molecules and structures that could eventually be targeted for therapies.”
Over the course of a lifetime, 1 in 8 women will be diagnosed with breast cancer.
Risk factors a woman cannot change include:
- Age and gender: The risk of developing breast cancer increases as one ages. The majority of advanced breast cancer cases are found in women over age 50. Men can also get breast cancer; however, women are 100 times more likely to get breast cancer then men.
- Family history of breast cancer: A woman may also have a higher risk for breast cancer if she has a close relative who has had breast, uterine, ovarian, or colon cancer. About 20-30% of women with breast cancer have a family history of the disease.
- Genetic factors: Some women have genes that make them more prone to developing breast cancer. The most common gene defects are found in the BRCA1 and BRCA2 genes. These normally produce proteins that protect an individual from cancer. However, if a woman inherits a defective gene, she has an increased risk for breast cancer. Women with one of these defects have up to an 80% chance of getting breast cancer sometime during their life.
- Menstrual cycle: Women who begin menstruating at an early age (before age 12) or go through menopause late (after age 55) have an increased risk for breast cancer
Other risk factors include:
- Alcohol use: Drinking more than 1 - 2 glasses of alcohol a day may increase the risk of breast cancer.
- Childbirth: Women who have never had children or who had them only after age 30 have an increased risk for breast cancer. Being pregnant more than once or becoming pregnant at an early age reduces the risk of breast cancer.
- DES: Women who took diethylstilbestrol (DES) to prevent miscarriage may have an increased risk of breast cancer after age 40. This drug was given to the women in the 1940s through the 1960s.
- Hormone replacement therapy (HRT): Women who received hormone replacement therapy for several years or more may be at increased risk.
- Obesity: Obesity has been linked to breast cancer; however, this link is controversial. The theory is that obese women produce more estrogen, which can fuel the development of breast cancer.
- Radiation: Women who received radiation therapy as a child or young adult to treat cancer of the chest area have a significantly higher risk for developing breast cancer. The younger the radiation was started and the higher the dose, the higher the risk; radiation given during the time of breast development produces the highest risk.
Breast cancer myths:
Breast implants, using antiperspirants, and wearing underwire bras do not increase the risk for breast cancer. There is no evidence of a direct link between breast cancer and pesticides.
Reference: UC Berkeley
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