Journal
MOLECULAR CANCER RESEARCH
Volume 14, Issue 4, Pages 344-353Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1541-7786.MCR-15-0466
Keywords
-
Categories
Funding
- Stand Up to Cancer-Prostate Cancer Foundation-Prostate Dream Team Translational Cancer Research Grant [SU2C-AACR-DT0812]
- UCLA SPORE in Prostate Cancer
- Department of Defense Prostate Cancer Research Program [W81XWH-11-1-0227, W81XWH-12-1-0206]
- NIH [1R01CA158627-01, 1R01CA172603-01A1]
- Prostate Cancer Foundation Honorable A. David Mazzone Special Challenge Award
- Stand-up-to-Cancer Dream Team Award
- National Natural Science Foundation of China [81460387]
Ask authors/readers for more resources
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. (C) 2016 AACR.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available