Endoplasmic reticulum Ca2+-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) Ca2+-homeostasis is different in lung cancer and normal human bronchial epithelial (NHBE) cells.


METHODS
The intracellular Ca2+-signaling was investigated using fluorescence microscopy and the expression of Ca2+-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 Ca2+-content was reduced compared to NHBE. The reduced Ca2+-content correlated with a reduced expression of SERCA 2 pumping calcium into the ER, an increased expression of IP3R releasing calcium from the ER, and a reduced expression of calreticulin buffering calcium within the ER. Lowering the ER Ca2+-content with CPA led to increased proliferation NHBE and lung cancer cells.


CONCLUSIONS
The significant differences in Ca2+-homeostasis between lung cancer and NHBE cells could represent a new target for cancer treatments.
Bergner
Albrecht
A
Division of Respiratory Medicine, Medizinische Klinik-Innenstadt, Ludwig-Maximilians-University, Munich, Germany. albrecht.bergner@med.uni-muenchen.de
Kellner
Julia
J
Tufman
Amanda
A
Huber
Rudolf M
RM
D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D055752:Small Cell Lung Carcinoma / Q000378:metabolism*
D002135:Calcium-Binding Proteins; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium