Siewe Nourridine, Friedman Avner
School of Mathematical Sciences, College of Science, Rochester Institute of Technology, Rochester, NY, USA.
Department of Mathematics, The Ohio State University, Columbus, OH, USA.
Bull Math Biol. 2023 Jan 6;85(2):12. doi: 10.1007/s11538-022-01117-0.
Pre-metastatic niche is a location where cancer cells, separating from a primary tumor, find "fertile soil" for growth and proliferation, ensuring successful metastasis. Exosomal miRNAs of breast cancer are known to enter the bone and degrade it, which facilitates cancer cells invasion into the bone interior and ensures its successful colonization. In this paper, we use a mathematical model to first describe, in health, the continuous remodeling of the bone by bone-forming osteoblasts, bone-resorbing osteoclasts and the RANKL-OPG-RANK signaling system, which keeps the balance between bone formation and bone resorption. We next demonstrate how breast cancer exosomal miRNAs disrupt this balance, either by increasing or by decreasing the ratio of osteoclasts/osteoblasts, which results in abnormal high bone resorption or abnormal high bone forming, respectively, and in bone weakening in both cases. Finally we consider the case of abnormally high resorption and evaluate the effect of drugs, which may increase bone density to normal level, thus protecting the bone from invasion by cancer cells.
前转移微环境是一个位置，在这个位置，从原发性肿瘤分离出来的癌细胞找到用于生长和增殖的“肥沃土壤”，确保成功转移。已知乳腺癌的外泌体微小核糖核酸（miRNAs）进入骨骼并使其降解，这有助于癌细胞侵入骨内部并确保其成功定植。在本文中，我们首先使用一个数学模型来描述在健康状态下，成骨的成骨细胞、骨吸收的破骨细胞以及RANKL-OPG-RANK信号系统对骨骼的持续重塑，该系统保持骨形成和骨吸收之间的平衡。接下来，我们展示乳腺癌外泌体微小核糖核酸如何通过增加或降低破骨细胞/成骨细胞的比例来破坏这种平衡，这分别导致异常高的骨吸收或异常高的骨形成，并且在两种情况下都会导致骨骼变弱。最后，我们考虑异常高吸收的情况，并评估药物的效果，这些药物可能会将骨密度提高到正常水平，从而保护骨骼免受癌细胞的侵袭。
