Abstract
Cancer is associated with increased fracture risk, due either to metastasis or associated osteoporosis. After a fracture, blood clots form. Because proteins of the coagulation cascade and activated platelets promote cancer development, a fracture in patients with cancer often raises the question whether it is a pathologic fracture or whether the fracture itself might promote the formation of metastatic lesions. We therefore examined whether blood clot formation results in increased metastasis in a murine model of experimental breast cancer metastasis.For this purpose, a clot was surgically induced in the bone marrow of the left tibia of immundeficient mice. Either one minute prior to or five minutes after clot induction, human cancer cells were introduced in the circulation by intracardiac injection. The number of cancer cells that homed to the intervention site was determined by quantitative real-time PCR and flow cytometry. Metastasis formation and longitudinal growth were evaluated by bioluminescence imaging.The number of cancer cells that homed to the intervention site after 24 hours was similar to the number of cells in the opposite tibia that did not undergo clot induction. This effect was confirmed using two more cancer cell lines. Furthermore, no difference in the number of macroscopic lesions or their growth could be detected. In the control group 72% developed a lesion in the left tibia. In the experimental groups with clot formation 79% and 65% developed lesions in the left tibia (p = ns when comparing each experimental group with the controls). Survival was similar too.In summary, the growth factors accumulating in a clot/hematoma are neither enough to promote cancer cell homing nor support growth in an experimental model of breast cancer bone metastasis. This suggests that blood clot formation, as occurs in traumatic fractures, surgical interventions, and bruises, does not increase the risk of metastasis formation.
Highlights
Breast and prostate cancer represent the most common solid tumors in adults associated with bone metastasis [1]
We found neither an increase in the number of cancer cells localized to the clot nor an increase in the number of metastatic lesions developing in the injured left tibia
Intratibial hematoma and clot formation In order to determine whether the model we contemplated using resulted in the development of a blood clot within the bone marrow, we performed the procedure of intratibial bone marrow flushing in mice and examined the tibiae 5 and 60 minutes, as well as 24, 48 and 72 hours after the end of the procedure
Summary
Breast and prostate cancer represent the most common solid tumors in adults associated with bone metastasis [1]. These metastases originate from circulating cancer cells that hijack the hematopoietic stem cell niches in the bone marrow taking advantage of its unique richness in cytokines [2,3,4]. The growth of a metastatic lesion in the bone often increases the risk of a pathologic fracture [5,6]. The question occasionally arises as to whether the occurrence of a fracture in a patient with cancer is a reflection of the presence of a metastatic lesion at the fracture site or whether the pathologic processes that take place in the event of a fracture increase the risk of establishment of tumor cells at the site of the fracture
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