Human pancreatic cancer tumors are nutrient poor and tumor cells actively scavenge extracellular protein

Cancer Research

Volumn 75, Issue 3, 2015, Pages 544-553

  Kamphorst, Jurre J ^a,g   Nofal, Michel ^a   Commisso, Cosimo ^b,h   Hackett, Sean R ^a   Lu, Wenyun ^a   Grabocka, Elda ^b   Vander Heiden, Matthew G ^c,d   Miller, George ^b   Drebin, Jeffrey A ^e   Bar Sagi, Dafna ^b   Thompson, Craig B ^f   Rabinowitz, Joshua D ^a  

^a PRINCETON UNIVERSITY   (United States)

^b NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^d DANA FARBER CANCER INSTITUTE   (United States)

^e HOSPITAL OF THE UNIVERSITY OF PENNSYLVANIA   (United States)

^f MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^g UNIVERSITY OF GLASGOW   (United Kingdom)

^h BURNHAM INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALBUMIN; CREATINE PHOSPHATE; CYTIDINE; EXTRACELLULAR PROTEIN; GLUCOSE; GLUCOSE 6 PHOSPHATE; GLUTAMINE; GLYCEROPHOSPHATE; GUANIDINOACETIC ACID; ISOLEUCINE; LEUCINE; PEPTIDES AND PROTEINS; SERINE; TRANSKETOLASE; TRYPTOPHAN; UNCLASSIFIED DRUG; VALINE; ALBUMINOID; AMINO ACID;

AMINO ACID SYNTHESIS; AMINO ACID TRANSPORT; ANIMAL CELL; APOPTOSIS; ARTICLE; BIOACCUMULATION; CELL LEVEL; CELL PROLIFERATION; CELL SURVIVAL; CELLULAR, SUBCELLULAR AND MOLECULAR BIOLOGICAL PHENOMENA AND FUNCTIONS; CLINICAL ARTICLE; COMPARATIVE STUDY; CONTROLLED STUDY; CULTURE MEDIUM; CULTURE TECHNIQUE; EX VIVO STUDY; FALSE NEGATIVE RESULT; FALSE POSITIVE RESULT; HUMAN; HUMAN CELL; HUMAN TISSUE; ISOTOPE LABELING; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; METABOLOME; METABOLOMICS; MOLECULAR DYNAMICS; MOUSE; NONHUMAN; NUTRIENT UPTAKE; PANCREAS ADENOCARCINOMA; PINOCYTOSIS; PROTEIN DEGRADATION; PROTEIN SCAVENGING; PROTEIN SYNTHESIS; TUMOR CELL; TUMOR GROWTH; ANIMAL; CHEMISTRY; CYTOLOGY; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; PANCREAS CARCINOMA; PANCREAS TUMOR; SIGNAL TRANSDUCTION; STEM CELL; TUMOR CELL CULTURE;

ALBUMINS; AMINO ACIDS; ANIMALS; CARCINOMA, PANCREATIC DUCTAL; CELL PROLIFERATION; CHROMATOGRAPHY, LIQUID; GENE EXPRESSION REGULATION, NEOPLASTIC; GLUCOSE; GLUTAMINE; HUMANS; MASS SPECTROMETRY; MICE; PANCREATIC NEOPLASMS; PINOCYTOSIS; SERINE; SIGNAL TRANSDUCTION; STEM CELLS; TUMOR CELLS, CULTURED;

EID: 84961288972     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-14-2211     Document Type: Article

References (34)

1. Hidalgo M. Pancreatic cancer. N Engl J Med 2010;362:1605-17.
2. Biankin AV, Waddell N, Kassahn KS, Gingras MC, Muthuswamy LB, Johns AL, et al. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature 2012;491:399-405.
3. Ying H, Kimmelman AC, Lyssiotis CA, Hua S, Chu GC, Fletcher-Sananikone E, et al. Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell 2012;149:656-70.
4. Vander Heiden MG, Lunt SY, Dayton TL, Fiske BP, Israelsen WJ, Mattaini KR, et al. Metabolic pathway alterations that support cell proliferation. Cold Spring Harb Symp Quant Biol 2011;76:325-34.
5. Fan J, Kamphorst JJ, Mathew R, Chung MK, White E, Shlomi T, et al. Glutamine-driven oxidative phosphorylation is a major ATP source in transformed mammalian cells in both normoxia and hypoxia. Mol Syst Biol 2013;9:712.
6. Gaglio D, Metallo CM, Gameiro PA, Hiller K, Danna LS, Balestrieri C, et al. Oncogenic K-Ras decouples glucose and glutaminemetabolism to support cancer cell growth. Mol Syst Biol 2011;7:523-38.
7. Son JJ, Lyssiotis CA, Ying H, Wang X, Hua S, Ligorio M, et al. Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature 2013;496:101-5.
8. Yun J, Rago C, Cheong I, Pagliarini R, Angenendt P, Rajagopalan H, et al. Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells. Science 2009;325:1555-9.
9. Duffy JP, Eibl G, Reber HA, Hines OJ. Influence of hypoxia and neoangiogenesis on the growth of pancreatic cancer. Mol Cancer 2003;2:12.
10. Koong AC, Mehta VK, Le QT, Fisher GA, Terris DJ, Brown JM, et al. Pancreatic tumors show high levels of hypoxia. Int J Radiat Oncol Biol Phys 2000;48:919-22.
11. Roberts E, Tanaka T. Free amino acids of the Yoshida ascites tumor. Cancer Res 1956;16:204-10.
12. Roberts E, Frankel S. Free amino acids in normal and neoplastic tissues of mice as studied by paper chromatography. Cancer Res 1949;9:645-8.
13. Bar-Sagi D, Feramisco JR. Induction of membrane ruffling and fluid-phase pinocytosis in quiescent fibroblasts by Ras proteins. Science 1986;233:1061-8.
14. Commisso C, Davidson SM, Soydaner-Azeloglu RG, Parker SJ, Kamphorst JJ, Hackett S, et al. Macropinocytosis as a mechanism of glutamine supply in Ras transformed cancer cells. Nature 2013;497:633-7.
15. Stehle G, Sinn H, Wunder A, Schrenk HH, Stewart JCM, Hartung G, et al. Plasma protein (albumin) catabolism by the tumor itself - implications for tumor metabolism and the genesis of cachexia. Crit Rev Oncol Hematol 1997;26:77-100.
16. Lito P, Saborowski A, Yue J, Solomon M, Joseph E, Gadal S, et al. Disruption of CRAF-mediated MEK activation is required for effective MEK inhibition in KRAS mutant tumors. Cancer Cell 2014;25:697-710.
17. Lu W, Clasquin MF, Melamud E, Amador-Noguez D, Caudy AA, Rabinowitz JD. Metabolomic analysis via reversed-phase ion-pairing liquid chromatography coupled to a stand alone orbitrap mass spectrometer. Anal Chem 2010;82:3212-21.
18. Bajad SU, Lu W, Kimball EH, Yuan J, Peterson C, Rabinowitz JD. Separation and quantitation of water soluble cellular metabolites by hydrophilic interaction chromatography-tandem mass spectrometry. J Chromatogr A 2006;1125:76-88.
19. Melamud E, Vastag L, Rabinowitz JD. Metabolomic analysis and visualization engine for LC-MS data. Anal Chem 2010;82:9818-26.
20. Pesek JJ, Matyska MT, Fischer SM, Sana TR. Analysis of hydrophilic metabolites by high-performance liquid chromatography-mass spectrometry using a silica hydride-based stationary phase. J Chromatogr A 2008;1204:48-55.
21. Commisso C, Flinn RJ, Bar-Sagi D. Determining the macropinocytic index of cells through a quantitative image-based assay. Nat Protoc 2014;9:182-92.
22. Efron B, Tibshirani R. Bootstrap methods for standard errors, confidence intervals, and othermeasures of statistical accuracy. Stat Sci 1986;1:54-75.
23. Storey JD, Tibshirani R. Statistical significance for genomewide studies. Proc Natl Acad Sci U S A 2003;100:9440-5.
24. Wollenberger A, Ristau O, Schoffa G. [Eine einfache Technik der extrem schnellen Abkuhlung grosserer Gewebestucke]. Pflugers Archiv 1960;270:399-412.
25. Quistorff B, Pedersen E. A new device for the freeze-clamping of tissue samples. Anal Biochem 1976;73:236-9.
26. González A, Varo N, Alegre E, Díaz A, Melero I. Immunosuppression routed via the kynurenine pathway: a biochemical and pathophysiologic approach. Adv Clin Chem 2008;45:155-97.
27. Yoshimori T, Yamamoto A, Moriyama Y, Futai M, Tashiro Y. Bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase, inhibits acidification and protein degradation in lysosomes of cultured cells. J Biol Chem 1991;266:17707-12.
28. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009;324:1029-33.
29. Higashi T, Saga T, Nakamoto Y, Ishimori T, Fujimoto K, Doi R, et al. Diagnosis of pancreatic cancer using fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET)- usefulness and limitations in "clinical reality."Ann Nucl Med 2003;17:261-79.
30. Chu GC, Kimmelman AC, Hezel AF, DePinho RA. Stromal biology of pancreatic cancer. J Cell Biochem 2007;101:887-907.
31. Kamphorst JJ, Cross JR, Fan J, de Stanchina E, Mathew R, White EP, et al. Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids. Proc Natl Acad Sci U S A 2013;110:8882-7.
32. Yang S, Wang X, Contino G, Liesa M, Sahin E, Ying H, et al. Pancreatic cancers require autophagy for tumor growth. Genes Dev 2011;25:717-29.
33. Guo JY, Chen HY, Mathew R, Fan J, Strohecker AM, Karsli-Uzunbas G, et al. Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis. Genes Dev 2011;25:460-70.
34. Von Hoff DD, Ramanathan RK, Borad MJ, Laheru DA, Smith LS, Wood TE, et al. Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer: a phase I/II trial. J Clin Oncol 2011;29:4548-54.