title: The Role of CD44 in Glucose Metabolism in Prostatic Small Cell Neuroendocrine Carcinoma.
abstract: 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 reactive oxygen species (ROS) levels, we performed metabolic profiling in these two model systems. The role of CD44 was studied by 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 versus 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 biologic behaviors of these two tumor types.
  
  
  CONCLUSIONS
  CD44 is an important regulator of glucose metabolism in small cell neuroendocrine carcinoma and may be an important therapeutic target.
authors.affiliation: Departments of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California. Department of Urology, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Departments of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
authors.forename: Alexa
authors.initials: A
authors.lastname: Cohen
authors.affiliation: Departments of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California. Department of Radiation Oncology, University of Rochester Medical Center School of Medicine and Dentistry, Rochester, New York.
authors.forename: Yin
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Departments of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
authors.forename: Jill
authors.initials: J
authors.lastname: Squires
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California. UCLA Metabolomics Center, University of California Los Angeles, Los Angeles, California.
authors.forename: Daniel
authors.initials: D
authors.lastname: Braas
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California. UCLA Metabolomics Center, University of California Los Angeles, Los Angeles, California. Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California. Crump Institute for Molecular Imaging, University of California Los Angeles, Los Angeles, California.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Graeber
authors.affiliation: Department of Biostatistics, Jonsson Comprehensive Cancer Center Biostatistics/BASE Unit, School of Public Health at UCLA, Los Angeles, California.
authors.forename: Lin
authors.initials: L
authors.lastname: Du
authors.affiliation: Department of Biostatistics, Jonsson Comprehensive Cancer Center Biostatistics/BASE Unit, School of Public Health at UCLA, Los Angeles, California.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Departments of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California. Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Departments of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California. School of Life Sciences, Anhui University, Hefei, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Xu
authors.affiliation: Departments of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
authors.forename: Xufeng
authors.initials: X
authors.lastname: Chen
authors.affiliation: Departments of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California. Jiaoti.huang@duke.edu.
authors.forename: Jiaoti
authors.initials: J
authors.lastname: Huang
mesh_terms: D018278:Carcinoma, Neuroendocrine / Q000378:metabolism*; D018288:Carcinoma, Small Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D025481:Phosphofructokinase-2 / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D046888:Tissue Array Analysis / Q000379:methods
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C506672:PFKFB4 protein, human; D017382:Reactive Oxygen Species; D019344:Lactic Acid; D025481:Phosphofructokinase-2; D005947:Glucose
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