The related tendency in the expression pattern in tumor tissue and RCC cells almost the same 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 benefits indicate a calcium dependence of bone metastasis in RCC, as currently defined within the major tumor by CaSR expression. Due to the fact RCC metastasis shows an osteolytic property immediately after initiating bone metastasis, the calcium concentration rises because of bone resorption, which in turn results in an additional improve of the metastatic po tential of RCC cells. CaSR seems 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 throughout cultivation that advocates further investigation in vitro employing main cells. Therapy of RCC cells with calcium had no influ ence around the expression of CaSR, indicating that calcium can kinase inhibitor EPZ-5676 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 due to the fact that calcium injected in to the inferior vena cava of rats didn’t drastically alter the CaSR expression inside the parathyroid gland or within the kidney. Essential actions in metastasis would be the migration of tumor cells and cell proliferation inside the secondary organ.
In this study the influence of calcium on these two methods was analyzed as a way to imitate selleck chemicalsNMS-873 the calcium conditions in the bone microenvironment. In RCC cells metastasizing into bones and expressing a high degree of CaSR, the che motactical potential of calcium was 19 fold larger than in non metastasizing cells. The CaSR inhibitor NPS 2143 rescinded this effect, evidencing the value of CaSR in the calcium dependent reaction.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 hence 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 outcomes, in colon carcinoma cells and neuroblastoma cells, calcium and activation in the CaSR have been shown to inhibit proliferation and induce apoptosis, indicating CaSR as a tumor suppres sor. The effect of calcium and activation of CaSR seem to become dependent on cell sort and have to be regarded as tissue distinct.