Stimulating effect of wound healing on dormant breast cancer
Breast cancer is known for its ability to metastasize early, even before clinical diagnosis. The micrometastases may then enter a state of dormancy with no growth. Upon stimulation, the cells may escape from dormancy and cause overt, incurable metastatic disease. Tissue trauma and wound healing has been suggested to constitute such a stimulating event. We wish to explore this relationship in a mouse model with systemically disseminated dormant breast cancer cells. The animals will be subject to mastectomy, analogous to actual events in human patients, and subsequently evaluated for metastases formation. Organs and metastases will, after euthanasia, be analyzed for markers of escape from dormancy, angiogenesis, proliferation and immune cell infiltration. As surgery still remains a cornerstone in the treatment of breast cancer, a detailed understanding of the mechanisms responsible for this connection could open new therapeutic possibilities to prevent tumor stimulating effects and metastatic disease. We plan to use 76 female BALB/c mice.
3Rs:
As we are interested in the systemic effects of factors released in tissue trauma and subsequent wound healing on tumor cells located at distant sites in multiple organs, an animal model is necessary to utilize, thus, replacement is not applicable.
A sample size calculation was performed to determine the minimum number of animals needed to obtain reliable results. Relative reduction is achieved by harvesting all organs and tumors for subsequent analysis.
Animals will be housed in groups in an enriched environment to allow for expression of natural behavior such as nesting. All surgical procedures and tumor implantation will be performed under general gas anesthesia by a scientist with training in surgery on mice. Animals will be systematically monitored for signs of pain, distress and tumor growth, As the cancer cell line to be tested is weakly metastatic, we do not expect symptoms of metastatic disease before the experiment is terminated and the mice euthanized. Post-surgery, analgesics will be administered subcutaneously day 0-1, after this upon indication. Humane endpoints will be monitored as defined in the attachment and animals will be euthanized if these are reached.
3Rs:
As we are interested in the systemic effects of factors released in tissue trauma and subsequent wound healing on tumor cells located at distant sites in multiple organs, an animal model is necessary to utilize, thus, replacement is not applicable.
A sample size calculation was performed to determine the minimum number of animals needed to obtain reliable results. Relative reduction is achieved by harvesting all organs and tumors for subsequent analysis.
Animals will be housed in groups in an enriched environment to allow for expression of natural behavior such as nesting. All surgical procedures and tumor implantation will be performed under general gas anesthesia by a scientist with training in surgery on mice. Animals will be systematically monitored for signs of pain, distress and tumor growth, As the cancer cell line to be tested is weakly metastatic, we do not expect symptoms of metastatic disease before the experiment is terminated and the mice euthanized. Post-surgery, analgesics will be administered subcutaneously day 0-1, after this upon indication. Humane endpoints will be monitored as defined in the attachment and animals will be euthanized if these are reached.