Endoplasmic reticulum Ca(2+)-homeostasis is altered in small and non-small cell lung cancer cell lines

BACKGROUND: Knowledge of differences in the cellular physiology of malignant and non-malignant cells is a prerequisite for the development of cancer treatments that effectively kill cancer without damaging normal cells. Calcium is a ubiquitous signal molecule that is involved in the control of proliferation and apoptosis. We aimed to investigate if the endoplasmic reticulum (ER) Ca(2+)-homeostasis is different in lung cancer and normal human bronchial epithelial (NHBE) cells. METHODS: The intracellular Ca(2+)-signaling was investigated using fluorescence microscopy and the expression of Ca(2+)-regulating proteins was assessed using Western Blot analysis. RESULTS: In a Small Cell Lung Cancer (H1339) and an Adeno Carcinoma Lung Cancer (HCC) cell line but not in a Squamous Cell Lung Cancer (EPLC) and a Large Cell Lung Cancer (LCLC) cell line the ER Ca(2+)-content was reduced compared to NHBE. The reduced Ca(2+)-content correlated with a reduced expression of SERCA 2 pumping calcium into the ER, an increased expression of IP(3)R releasing calcium from the ER, and a reduced expression of calreticulin buffering calcium within the ER. Lowering the ER Ca(2+)-content with CPA led to increased proliferation NHBE and lung cancer cells. CONCLUSION: The significant differences in Ca(2+)-homeostasis between lung cancer and NHBE cells could represent a new target for cancer treatments.