Pathways to Breast Cancer Bone Metastases Identified

Dr. Xiang (Shawn) Zhang PhD Assistant Professor Department of Molecular and Cellular Biology Lester and Sue Smith Breast Center Baylor College of Medicine Houston, TexasMedicalResearch.com Interview with:
Dr. Xiang (Shawn) Zhang PhD

Assistant Professor
Department of Molecular and Cellular Biology
Lester and Sue Smith Breast Center
Baylor College of Medicine Houston, Texas

 

Medical Research: What is the background for this study? What are the main findings?

Response: Bone metastases present a major clinical problem for oncologists. They are very painful and unpleasant due to the ability of metastatic cells to dissolve bones, and if they spread to the spine or vertebrate bone they  the spinal cord compression could cause paralysis. There is a gap in our knowledge about bone metastasis in breast cancer. We know a lot about when they are fully established and already dissolving the bone, but little about what happens early on, right after the cancer cells get there but before they start the bone-dissolving process.

In the study, we revealed that in the early stages, when there are only a few cancer cells, these cells tend to locate themselves in a microenvironment that is enriched in bone making cells called osteoblasts whose normal job is to help make new bones. The cancer cells appear to be surrounded by these bone-making cells before they acquire the ability to dissolve bones.

We also uncovered the pathway that gets activated when the cancer cells lodge into the bone-making cells, and helps them progress to more malignant metastases. The action is mediated by a class of proteins that helps bind the cancer cells to the bone tissue called heterotypic adherens junctions (hAJs) involving the adherens proteins E-cadherin (cancer-derived) and N-cadherin (bone-promoting). This then activates the mTOR pathway in cancer cells, which drives the progression from single cells to metastases.

Medical Research: What should clinicians and patients take away from your report?

Response: We need new targeted therapies for breast cancer that has spread to the bone. So far, we have certain drugs that can delay progression but the overall survival has not improved, The hAJs may be a very unique target. We may be able to block the communication between cancer cells and bone-making cells, thereby preventing the onset of bone metastasis. We hope this may be useful in the future to reduce the occurrence of the painful bone-dissolving metastases.

Medical Research: What recommendations do you have for future research as a result of this study?

Response: Several avenues are opened by this study.

First, the fact that bone-making cells can help cancer cells in the early stage suggest a link between normal bone regeneration and bone metastasis. This is of great clinical relevance as it may reveal wound-healing, osteoporosis and other bone pathological conditions as risk factors of breast cancer bone metastasis.

Second, it remains unknown how cancer cells and bone-making cells attract each other and get together. This attraction mechanism will also be a key target that may be used to prevent bone metastasis.

Third, how bone metastases gain their bone-dissolving ability and transit into the more malignant and painful stage needs more research. This is another therapeutic window that may control bone metastasis progression. Finally, we need to find a sensitive biomarker to distinguish patients that are likely to develop bone metastases. These are the patients with cancer cells already disseminated to the bone but not yet exhibit overt bone metastasis symptoms.  New techniques are required to detect the trace of these hidden cancer cells.

Citation:

Cancer Cell. 2015 Jan 14. pii: S1535-6108(14)00468-1. doi: 10.1016/j.ccell.2014.11.017. [Epub ahead of print]

The Osteogenic Niche Promotes Early-Stage Bone Colonization of Disseminated Breast Cancer Cells.

Wang H1, Yu C1, Gao X1, Welte T1, Muscarella AM2, Tian L3, Zhao H4, Zhao Z5, Du S6, Tao J7, Lee B7, Westbrook TF8, Wong ST9, Jin X10, Rosen JM11, Osborne CK12, Zhang XH13

 

MedicalResearch.com Interview with:, & Dr. Xiang (Shawn) Zhang PhD (2015). Pathways to Breast Cancer Bone Metastases Identified MedicalResearch.com