Project Details
Description
Breast cancer shows preference for homing to bone marrow where the cancer cells adapt a quiet phase, referred to as dormancy. This phase fits with the clinical evidence that breast cancer can arise from bone marrow after more than 10 years of the oncologist telling the patient that she/he or has been in remission. It is unlikely that the cancer cells select the bone marrow. Rather, we believe that cancer cells enter several organs, but when they reach the bone marrow cavity, they use the properties of the bone marrow microenvironment for their survival. This innovative grant plans to examine small RNA, referred to as microRNA (miRNA), within small particles called exosomes in the dormancy of cancer cells in bone marrow. We have already proved that dormancy is partly caused by the cancer cells forming tight connection with the stromal cells of bone marrow. The close and tight connection causes miRNAs to move from the cancer cells to stroma. This movement of small RNA sets up a series of reactions to quiet the cancer cells. The concept proposes that miRNA can be released from stroma inside of small particles called exosomes, which transfer to the cancer cells. In addition, the exosomes can also be released from one of the stem cells in bone marrow: mesenchymal stem cells (MSCs). We have divided breast cancer cells into two categories: those that show property of stem cells and those that cycle and are generated from those that resemble stem cells. The hypothesis to be tested states that exosomes released from stroma and/or MSCs contain two types of miRNAs (miR-222 and miR-223) and these enter the stem cell line cancer cells to make them remain quiet. To test the hypothesis, we will first determine the levels of miRNA-222 and miR-223 in the exosomes and then investigate if different cells release their particular type of exosomes. Second, we plan to determine if the cancer cells are required to be close to the other cells type for the exosomes to be able to enter the cancer cells. Overall, this grant is highly significant in light of the bone marrow remaining as a major clinical problem: being a major site of breast cancer resurgence even after more than 10 years of remission. Additionally, this concept is relevant to breast cancer in other regions since MSCs can home to the area of the cancer where they form tumor stroma.
Status | Finished |
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Effective start/end date | 5/1/11 → 4/30/14 |
Funding
- Congressionally Directed Medical Research Programs: $102,160.00