While prostatic adenocarcinomas are relatively indolent, some patients with advanced adenocarcinomas recur with small cell neuroendocrine carcinoma which is highly aggressive and lethal. Because glycolysis is a feature of malignancy and the degree of glycolysis generally correlates with tumor aggressiveness, we wanted to compare the metabolic differences and the molecular mechanisms involved between the two tumor types.
In this study, and based on previous characterization, LNCaP and PC-3 prostate cancer cell lines were selected as models of prostatic adenocarcinoma and small cell neuroendocrine carcinoma, respectively. In addition to measuring glucose consumption, lactate secretion, and ROS levels we performed metabolic profiling in these two model systems. The role of CD44 was studied by RNA interference (RNAi) and lentivirus-mediated overexpression. Expression of key enzymes in glycolysis was studied using human tissue microarrays containing benign prostate, adenocarcinoma, and small cell neuroendocrine carcinoma. Results showed that glycolytic features of PC-3 cells were higher than that of LNCaP cells. PFKFB4 was overexpressed in human small cell carcinoma tissue vs. adenocarcinoma tissue. CD44 regulated glucose metabolism, intracellular ROS, and cell proliferation in PC-3 cells. Inhibition of CD44 also sensitized PC-3 cells to carboplatin. In conclusion, this study suggests different pathways of glucose metabolism contribute to the disparate biological behaviors of these two tumor types.
CD44 is an important regulator of glucose metabolism in small cell neuroendocrine carcinoma and may be an important therapeutic target.
Molecular cancer research : MCR. 2016 Feb 01 [Epub ahead of print]
Wei Li, Alexa Cohen, Yin Sun, Jill Squires, Daniel Braas, Thomas G Graeber, Lin Du, Gang Li, Zhen Li, Xiang Xu, Xufeng Chen, Jiaoti Huang
Department of Urology, The People's Hospital of Guangxi Zhuang Autonomous Region. , Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles. , Department of Radiation Oncology, University of Rochester Medical Center School of Medicine and Dentistry. , Departments of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles. , UCLA Metabolomics Center, University of California Los Angeles. , Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles. , Crump Institute for Molecular Imaging, University of California Los Angeles. , Department of Biostatistics, School of Public Health at UCLA, Jonsson Comprehensive Cancer Center Biostatistics/BASE Unit. , Medical Oncology, Rutgers Cancer Institute of New Jersey. , School of Life Sciences, Anhui University. , Departments of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles. , Departments of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles