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The Role of CD44 in Glucose Metabolism in Prostatic Small Cell Neuroendocrine Carcinoma.

Publication ,  Journal Article
Li, W; Cohen, A; Sun, Y; Squires, J; Braas, D; Graeber, TG; Du, L; Li, G; Li, Z; Xu, X; Chen, X; Huang, J
Published in: Mol Cancer Res
April 2016

UNLABELLED: 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. IMPLICATIONS: CD44 is an important regulator of glucose metabolism in small cell neuroendocrine carcinoma and may be an important therapeutic target.

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Published In

Mol Cancer Res

DOI

EISSN

1557-3125

Publication Date

April 2016

Volume

14

Issue

4

Start / End Page

344 / 353

Location

United States

Related Subject Headings

  • Tissue Array Analysis
  • Reactive Oxygen Species
  • Prostatic Neoplasms
  • Phosphofructokinase-2
  • Oncology & Carcinogenesis
  • Male
  • Lactic Acid
  • Hyaluronan Receptors
  • Humans
  • Glycolysis
 

Citation

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Li, W., Cohen, A., Sun, Y., Squires, J., Braas, D., Graeber, T. G., … Huang, J. (2016). The Role of CD44 in Glucose Metabolism in Prostatic Small Cell Neuroendocrine Carcinoma. Mol Cancer Res, 14(4), 344–353. https://doi.org/10.1158/1541-7786.MCR-15-0466
Li, Wei, Alexa Cohen, Yin Sun, Jill Squires, Daniel Braas, Thomas G. Graeber, Lin Du, et al. “The Role of CD44 in Glucose Metabolism in Prostatic Small Cell Neuroendocrine Carcinoma.Mol Cancer Res 14, no. 4 (April 2016): 344–53. https://doi.org/10.1158/1541-7786.MCR-15-0466.
Li W, Cohen A, Sun Y, Squires J, Braas D, Graeber TG, et al. The Role of CD44 in Glucose Metabolism in Prostatic Small Cell Neuroendocrine Carcinoma. Mol Cancer Res. 2016 Apr;14(4):344–53.
Li, Wei, et al. “The Role of CD44 in Glucose Metabolism in Prostatic Small Cell Neuroendocrine Carcinoma.Mol Cancer Res, vol. 14, no. 4, Apr. 2016, pp. 344–53. Pubmed, doi:10.1158/1541-7786.MCR-15-0466.
Li W, Cohen A, Sun Y, Squires J, Braas D, Graeber TG, Du L, Li G, Li Z, Xu X, Chen X, Huang J. The Role of CD44 in Glucose Metabolism in Prostatic Small Cell Neuroendocrine Carcinoma. Mol Cancer Res. 2016 Apr;14(4):344–353.

Published In

Mol Cancer Res

DOI

EISSN

1557-3125

Publication Date

April 2016

Volume

14

Issue

4

Start / End Page

344 / 353

Location

United States

Related Subject Headings

  • Tissue Array Analysis
  • Reactive Oxygen Species
  • Prostatic Neoplasms
  • Phosphofructokinase-2
  • Oncology & Carcinogenesis
  • Male
  • Lactic Acid
  • Hyaluronan Receptors
  • Humans
  • Glycolysis