- Metastasis occurs when the cancer cells (for eg. in breast cancer) disseminate to other organs (like bones) after the elimination of the primary tumor.
- Cancer metastasis responds to therapies in a different manner from the primary tumor due to the distinct cancer-microenvironment in different organs.
- A new bone-in culture array has been developed that will help understand the interactions between metastatic breast cancer cells and bone cells and also the effect of different therapies in the growth of metastasis.
A new laboratory technique that can rapidly test the effectiveness of treatments for life-threatening breast cancer metastases in bone, has been developed by a team of researchers from the Baylor College of Medicine and other institutions.
"For a number of breast cancer patients, the problem is metastasis -- the dissemination of breast tumor cells to other organs -- after the primary tumor has been eliminated," said corresponding author Dr. Xiang Zhang, associate professor of molecular and cellular biology and the Lester and Sue Smith Breast Center at Baylor.
‘The new bone-in culture array can be used to understand the different mechanisms involved in bone colonization by cancer cells and to rapidly test drug efficacies on bone micrometastasis.’
Most of the primary breast tumors are usually surgically removed soon after diagnosis, leaving patients 'tumor-free'. But around 20%-40% of breast cancer survivors will eventually suffer metastasis to distant organs, sometimes years after surgery. Bone is the main organ of metastasis in case of breast cancer.
Metastasis is the dispersed metastatic seeds, which have disseminated to distant organs. They may be temporarily dormant, and may resume aggressive outgrowth under certain conditions.
"Metastases, however, tend to respond differently than the primary tumor to the treatment in part due to residing in a different organ with a different microenvironment." Zhang added.
Metastases are likely to differ from their parental primary tumors due adaptation in a different milieu.
The microenvironment in the distant organs plays an important role on deciding the disease progression and response to therapies.
The metastatic tumors have not been extensively investigated in their new microenvironment.
"We have created an experimental system in which we can mimic the interactions between cancer cells and bone cells, as bone is the place where breast cancer, and many other cancers too, disseminates most frequently," said Zhang, who also is a McNair Scholar at Baylor. "We have developed a system that allows us to test many different drug responses simultaneously to discover the therapy that can selectively act on metastatic cancer cells and minimize the effect on the bone."
For the investigation, a model of the bone metastasis called the cone-in culture array (BICA) was developed in the lab using fragmenting mouse bones that already contain breast cancer cells. This model mimicked the interactions between metastatic breast cancer cells and bone cells.
The bone-in culture
maintains the microenvironmental characteristics of bone metastasis in living animal models, and the cancer cells
maintain the gene expression profile, the growth pattern and their response to therapies.
Using the bone-in model, it was revealed that a drug danusertib preferentially inhibits bone metastasis. Certain other drugs were found to stimulate the growth of slow-growing cancer cells in the bone.
The bone-in culture can be used to :
- determine the effect of drugs in the growth of metastasis
- investigate mechanisms involved in the bone colonization by cancer cells
"We think that this new system has the potential to be applied not only to breast cancer but to other cancers that also metastasize to the bone," Zhang said. "This technique can be scaled up to larger sample sizes, which would help accelerate the process of discovering metastatic cancer treatments. We have already found a few interesting drugs. We will keep looking for more and focus on those that are most promising."
Future research plans include standardization of the system in order to develop drugs that can help treat metastatic cancer.
The study appears in Nature Communications
- Xiang Zhang et al. Bone-in-culture array as a platform to model early-stage bone metastases and discover anti-metastasis therapies. Nature Communications; (2017) doi:10.1038/ncomms15045