The comparable tendency in the expression pattern in tumor tissue and RCC cells nearly the identical as in non metastasizing cells. This indi cates a CaSR dependent chemotactical attraction of cal cium in bones inducing bone metastasis of RCC. Also cell proliferation of bone metastasizing RCC cells, in contrast to non or lung metastasizing cells, was extremely sensitive to calcium, dependent on CaSR. These final results indicate a calcium dependence of bone metastasis in RCC, as currently defined inside the main tumor by CaSR expression. Given that RCC metastasis shows an osteolytic home just after initiating bone metastasis, the calcium concentration rises on account of bone resorption, which in turn leads to an further increase from the metastatic po tential of RCC cells. CaSR appears to also play a part in cancer progression of other entities.
In bone metastatic breast and prostate cancer cells, calcium and CaSR induces proliferation and shows a stability of this attribute in the course of cultivation that advocates further investigation in vitro using primary cells. Treatment mTOR activity of RCC cells with calcium had no influ ence on the expression of CaSR, indicating that calcium is usually excluded as a regulator for the expression of CaSR. These final results confirm the hypothesis of Rogers et al, who stated that calcium will not regulate the ex pression of CaSR as a result of the truth that calcium injected in to the inferior vena cava of rats didn’t significantly change the CaSR expression inside the parathyroid gland or within the kidney. Important measures in metastasis are the migration of tumor cells and cell proliferation in the secondary organ.
Within this study the influence of calcium on these two actions was analyzed to be able to imitate the calcium conditions in the bone microenvironment. In RCC cells metastasizing into bones and expressing a high level of CaSR, the che motactical potential of calcium was 19 fold larger than in non metastasizing cells. The CaSR inhibitor NPS 2143 selleck chemical PD-183805 rescinded this impact, evidencing the importance of CaSR within the calcium dependent reaction. In lung metas tasizing RCC cells, calcium dependent migration was motility. In parathyroid cancer, CaSR expression reduces Ki67 antigen level and thus is inversely cor related with cell proliferation. Also in astrocytoma cells and ovarian cells, CaSR activation in duced proliferation and functioned as an oncogene.
In contrast to these final results, in colon carcinoma cells and neuroblastoma cells, calcium and activation of the CaSR have already been shown to inhibit proliferation and induce apoptosis, indicating CaSR as a tumor suppres sor. The effect of calcium and activation of CaSR appear to be dependent on cell type and need to be deemed tissue particular. The CaSR is often a G protein coupled receptor activat ing several signaling pathways that are identified to regu late cell proliferation, differentiation, migration and apoptosis.