The related 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 highly sensitive to calcium, dependent on CaSR. These results indicate a calcium dependence of bone metastasis in RCC, as already defined in the main tumor by CaSR expression. Since RCC metastasis shows an osteolytic home after initiating bone metastasis, the calcium concentration rises resulting from bone resorption, which in turn results in an extra increase on the metastatic po tential of RCC cells. CaSR seems to also play a role 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 additional investigation in vitro utilizing main cells. Treatment of RCC cells with calcium had no influ ence on the expression of CaSR, indicating that calcium can selleck chemicals be 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 consequence of the truth that calcium injected in to the inferior vena cava of rats did not drastically alter the CaSR expression within the parathyroid gland or in the kidney. Crucial steps in metastasis would be the migration of tumor cells and cell proliferation within the secondary organ.
Within this study the influence of calcium on these two measures was analyzed so as to imitate PFI-1 ic50 the calcium situations inside the bone microenvironment. In RCC cells metastasizing into bones and expressing a high degree of CaSR, the che motactical possible of calcium was 19 fold larger than in non metastasizing cells. The CaSR inhibitor NPS 2143 rescinded this impact, evidencing the value of CaSR within the calcium dependent reaction.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 therefore is inversely cor associated with cell proliferation. Also in astrocytoma cells and ovarian cells, CaSR activation in duced proliferation and functioned as an oncogene. In contrast to these benefits, in colon carcinoma cells and neuroblastoma cells, calcium and activation on the CaSR have already been shown to inhibit proliferation and induce apoptosis, indicating CaSR as a tumor suppres sor. The impact of calcium and activation of CaSR seem to be dependent on cell variety and need to be regarded tissue certain.