Extracellular Regucalcin Suppresses the Growth, Migration, Invasion, and Adhesion of Metastatic Human Prostate Cancer Cells

Abstract

Regucalcin plays a multifunctional role in the regulation of cellular function including metabolism, signaling process and transcriptional activity in maintaining cell homeostasis. Downregulated expression or activity of regucalcin contributes to the development of malignancies in various types of human cancer. Survival of cancer patients, including metastatic prostate cancer, is prolonged with high expression of regucalcin in the tumor tissues. Furthermore, we elucidate whether extracellular regucalcin conquers the growth, migration, invasion and adhesion of metastatic human prostate cancer PC-3 and DU-145 cells. Extracellular regucalcin (0.1, 1, and 10 nM) of physiologic levels inhibited colony formation and growth of PC-3 and DU-145 cells, while it did not have an effect on cell death. Repressive effects of extracellular regucalcin on the proliferation were not exhibited by the presence of inhibitors of cell cycle, intracellular signaling process and transcriptional activity, suggesting that the signals of extracellular regucalcin are transmitted to block cell growth. Furthermore, extracellular regucalcin (0.1, 1, or 10 nM) inhibited migration, invasion and adhesion of PC-3 and DU-145 cells. Mechanistically, extracellular regucalcin (10 nM) decreased the levels of various signaling proteins including Ras, hosphatidylinositol-3 kinase, mitogen-activated protein kinase, mTOR, RSK-2, caveolin-1 and integrin β1 in PC-3 cells. Thus, extracellular regucalcin may play a suppressive role in growth, migration, invasion and adhesion, which are involved in metastatic activity of human prostate cancer cells, via affecting diverse signaling processes. This study may provide a new strategy in preventing metastatic prostate cancer with exogenous regucalcin.

Regucalcin Is a Potential Regulator in Human Cancer: Aiming to Expand into Cancer Therapy

“…Interestingly, extracellular regucalcin has been found to have suppressive effects on the growth, colony formation, migration, invasion, and adhesion of metastatic human prostate cancer PC-3 and DU-145 cells in vitro, as reported in [182]. The suppressive effects of extracellular regucalcin may result from a decrease in levels of multiple signaling proteins, such as Ras, phosphatidylinositol-3 kinase, MAP kinase, mTOR, RSK-2, caveolin-1, and integrin β1, in PC-3 cells [182]. This study demonstrated in vitro inhibition of metastatic activity by extracellular regucalcin.…”

“…A greater expression of regucalcin in tumor tissues extends the survival of patients with different cancer types. Recent studies have shown that extracellular regucalcin, found in the extracellular fluids of various tissues, suppresses the growth of several types of human cancer cells, such as HepG2 liver cancer cells [180], MiaPaCa-2 pancreatic cancer cells [179], MDA-MB-231 breast cancer cells [181], PC-3 prostate cancer cells [182], SK-OV-3 ovarian cancer cells [177], and Saos-2 osteosarcoma cells [161]. Extracellular regucalcin contributes to suppressing cancer cell growth in the cancer microenvironment.…”

“…of various tissues, suppresses the growth of several types of human cancer cells, such as HepG2 liver cancer cells [180], MiaPaCa-2 pancreatic cancer cells [179], MDA-MB-231 breast cancer cells [181], PC-3 prostate cancer cells [182], SK-OV-3 ovarian cancer cells [177], and Saos-2 osteosarcoma cells [161]. Extracellular regucalcin contributes to suppressing cancer cell growth in the cancer microenvironment.…”