Understanding the "lethal" drivers of tumor-stroma co-evolution: Emerging role(s) for hypoxia, oxidative stress and autophagy/mitophagy in the tumor micro-environment

Cancer Biology and Therapy

Volumn 10, Issue 6, 2010, Pages 537-542

  Lisanti, Michael P ^a,b,c,e   Martinez Outschoorn, Ubaldo E ^a,b,c   Chiavarina, Barbara ^a,c   Pavlides, Stephanos ^a,c   Whitaker Menezes, Diana ^a,c   Tsirigos, Aristotelis ^d   Witkiewicz, Agnieszka ^b   Lin, Zhao ^a,c   Balliet, Renee ^a,c   Howell, Anthony ^e   Sotgia, Federica ^a,c,e  

^a THOMAS JEFFERSON UNIVERSITY   (United States)

^b THOMAS JEFFERSON UNIVERSITY   (United States)

^c THOMAS JEFFERSON UNIVERSITY   (United States)

^d IBM T J WATSON RESEARCH CENTER   (United States)

^e UNIVERSITY OF MANCHESTER   (United Kingdom)

Author keywords

Aerobic glycolysis; Autophagy; Caveolin 1; HIF1; Hypoxia; Mitophagy; NF B; Oxidative stress; Reactive oxygen species (ROS); The "reverse Warburg effect"; TIGAR; Tumor stroma

Indexed keywords

ACETYLCYSTEINE; ANGIOGENESIS INHIBITOR; ANTINEOPLASTIC AGENT; ANTIOXIDANT; BEVACIZUMAB; BIOLOGICAL MARKER; CAVEOLIN 1; CHEMOATTRACTANT; CHLOROQUINE; DNA; HYPOXIA INDUCIBLE FACTOR 1ALPHA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; KETONE; LACTIC ACID; METFORMIN; QUERCETIN; REACTIVE OXYGEN METABOLITE; TRANSCRIPTION FACTOR;

AEROBIC CAPACITY; ANEUPLOIDY; ANTIANGIOGENIC THERAPY; ANTINEOPLASTIC ACTIVITY; ANTIOXIDANT ACTIVITY; APOPTOSIS; AUTOPHAGY; BIOGENESIS; BREAST CANCER; BYSTANDER EFFECT; CACHEXIA; CANCER CELL; CANCER CHEMOTHERAPY; CELL AGING; CELL COMPARTMENTALIZATION; CELL GROWTH; CELL HYPOXIA; CLINICAL TRIAL; DIET SUPPLEMENTATION; DNA DAMAGE; DRUG EFFICACY; ENERGY; FIBROBLAST; GENOMIC INSTABILITY; HETEROTROPHY; HUMAN; HYPOXIA; INFLAMMATION; LYMPH NODE METASTASIS; METABOLITE; METABOLOMICS; METASTASIS; MITOCHONDRION; MITOPHAGY; NEOPLASM; NONHUMAN; NUTRIENT; OVERALL SURVIVAL; OXIDATIVE STRESS; PROGNOSIS; RECEPTOR UPREGULATION; REVIEW; STROMA CELL; TUMOR GROWTH; TUMOR MICROENVIRONMENT;

ANIMALS; ANOXIA; AUTOPHAGY; CELL HYPOXIA; HUMANS; MODELS, BIOLOGICAL; NEOPLASMS; REACTIVE OXYGEN SPECIES; STROMAL CELLS; TUMOR MICROENVIRONMENT;

EID: 77957138161     PISSN: 15384047     EISSN: 15558576     Source Type: Journal    
DOI: 10.4161/cbt.10.6.13370     Document Type: Review

References (49)

1. Witkiewicz AK, Dasgupta A, Sotgia F, Mercier I, Pestell RG, Sabel M, et al. An Absence of stromal caveolin-1 expression predicts early tumor recurrence and poor clinical outcome in human breast cancers. Am J Pathol 2009; 174:2023-34.
2. Witkiewicz AK, Dasgupta A, Sammons S, Er O, Potoczek MB, Guiles F, et al. Loss of stromal caveolin-1 expression predicts poor clinical outcome in triple negative and basal-like breast cancers. Cancer Biol Ther 2010; 10:135-43.
3. Witkiewicz AK, Casimiro MC, Dasgupta A, Mercier I, Wang C, Bonuccelli G, et al. Towards a new "stromal-based" classification system for human breast cancer prognosis and therapy. Cell Cycle 2009; 8:1654-8.
4. Witkiewicz AK, Dasgupta A, Nguyen KH, Liu C, Kovatich AJ, Schwartz GF, et al. Stromal caveolin-1 levels predict early DCIS progression to invasive breast cancer. Cancer Biol Ther 2009; 8:1167-75.
5. Di Vizio D, Morello M, Sotgia F, Pestell RG, Freeman MR, Lisanti MP. An absence of stromal caveolin-1 is associated with advanced prostate cancer, metastatic disease and epithelial Akt activation. Cell Cycle 2009; 8:2420-4.
6. Martinez-Outschoorn UE, Pavlides S, Whitaker-Menezes D, Daumer KM, Milliman JN, Chiavarina B, et al. Tumor cells induce the cancer associated fibroblast phenotype via caveolin-1 degradation: Implications for breast cancer and DCIS therapy with autophagy inhibitors. Cell Cycle 2010; 9:2423-33.
7. Martinez-Outschoorn UE, Balliet RM, Rivadeneira DB, Chiavarina B, Pavlides S, Wang C, et al. Oxidative stress in cancer associated fibroblasts drives tumor-stroma co-evolution: A new paradigm for understanding tumor metabolism, the field effect and genomic instability in cancer cells. Cell Cycle 2010; 9:3256-76.
8. Martinez-Outschoorn UE, Trimmer C, Lin Z, Whitaker-Menezes D, Chiavarina B, Zhou J, et al. Autophagy in cancer associated fibroblasts promotes tumor cell survival: Role of hypoxia, HIF1 induction and NFκB activation in the tumor stromal microenvironment. Cell Cycle 2010; 9:3515-33.
9. Eng C, Leone G, Orloff MS, Ostrowski MC. Genomic alterations in tumor stroma. Cancer Res 2009; 69:6759-64.
10. Holliday C, Rummel S, Hooke JA, Shriver CD, Ellsworth DL, Ellsworth RE. Genomic instability in the breast microenvironment? A critical evaluation of the evidence. Expert Rev Mol Diagn 2009; 9:667-78.
11. Pavlides S, Tsirigos A, Migneco G, Whitaker-Menezes D, Chiavarina B, Flomenberg N, et al. The autophagic tumor stroma model of cancer: Role of oxidative stress and ketone production in fueling tumor cell metabolism. Cell Cycle 2010; 9:3485-505.
12. Pavlides S, Whitaker-Menezes D, Castello-Cros R, Flomenberg N, Witkiewicz AK, Frank PG, et al. The reverse Warburg effect: Aerobic glycolysis in cancer associated fibroblasts and the tumor stroma. Cell Cycle 2009; 8:3984-4001.
13. Bonuccelli G, Whitaker-Menezes D, Castello-Cros R, Pavlides S, Pestell RG, Fatatis A, et al. The reverse Warburg effect: Glycolysis inhibitors prevent the tumor promoting effects of caveolin-1 deficient cancer associated fibroblasts. Cell Cycle 2010; 9:1960-71.
14. Migneco G, Whitaker-Menezes D, Chiavarina B, Castello-Cros R, Pavlides S, Pestell RG, et al. Glycolytic cancer associated fibroblasts promote breast cancer tumor growth, without a measurable increase in angiogenesis: Evidence for stromal-epithelial metabolic coupling. Cell Cycle 2010; 9:2412-22.
15. Pavlides S, Tsirigos A, Vera I, Flomenberg N, Frank PG, Casimiro MC, et al. Loss of Stromal Caveolin-1 Leads to Oxidative Stress, Mimics Hypoxia and Drives Inflammation in the Tumor Microenvironment, Conferring the "Reverse Warburg Effect": A Transcriptional Informatics Analysis with Validation. Cell Cycle 2010; 9:2201-19.
16. Pavlides S, Tsirigos A, Vera I, Flomenberg N, Frank PG, Casimiro MC, et al. Transcriptional evidence for the "Reverse Warburg Effect" in human breast cancer tumor stroma and metastasis: similarities with oxidative stress, inflammation, Alzheimer's disease and "Neuron-Glia Metabolic Coupling". Aging 2010; 2:185-99.
17. Chiavarina B, Whitaker-Menezes D, Migneco G, Martinez-Outschoorn UE, Pavlides S, Howell A, et al. HIF1alpha functions as a tumor promoter in cancer associated fibroblasts and as a tumor suppressor in breast cancer cells: Autophagy drives compartment-specific oncogenesis. Cell Cycle 2010; 9:3534-51.
18. Bonuccelli G, Tsirigos A, Whitaker-Menezes D, Pavlides S, Pestell RG, Chiavarina B, et al. Ketones and lactate "fuel" tumor growth and metastasis: Evidence that epithelial cancer cells use oxidative mitochondrial metabolism. Cell Cycle 2010; 9:3506-14.
19. Garcia-Cardena G, Martasek P, Siler-Masters BS, Skidd PM, Couet JC, Li S, et al. Dissecting the interaction between nitric oxide synthase (NOS) and caveolin: Functional Significance of the NOS caveolin binding domain in vivo. J Biol Chem (Communication) 1997; 272:25437-40.
20. Warnold I, Lundholm K, Schersten T. Energy balance and body composition in cancer patients. Cancer Res 1978; 38:1801-7. (Pubitemid 8349732)
21. Bosaeus I, Daneryd P, Svanberg E, Lundholm K. Dietary intake and resting energy expenditure in relation to weight loss in unselected cancer patients. Int J Cancer 2001; 93:380-3.
22. Fouladiun M, Korner U, Bosaeus I, Daneryd P, Hyltander A, Lundholm KG. Body composition and time course changes in regional distribution of fat and lean tissue in unselected cancer patients on palliative care - correlations with food intake, metabolism, exercise capacity and hormones. Cancer 2005; 103:2189-98.
23. Norton JA, Peacock JL, Morrison SD. Cancer cachexia. Crit Rev Oncol Hematol 1987; 7:289-327.
24. Barber MD, Ross JA, Fearon KC. Cancer cachexia. Surg Oncol 1999; 8:133-41.
25. Droge W, Hack V, Breitkreutz R, Holm E, Shubinsky G, Schmid E, et al. Role of cysteine and glutathione in signal transduction, immunopathology and cachexia. Biofactors 1998; 8:97-102.
26. Hack V, Schmid D, Breitkreutz R, Stahl-Henning C, Drings P, Kinscherf R, et al. Cystine levels, cystine flux and protein catabolism in cancer cachexia, HIV/SIV infection and senescence. FASEB J 1997; 11:84-92.
27. Droge W, Gross A, Hack V, Kinscherf R, Schykowski M, Bockstette M, et al. Role of cysteine and glutathione in HIV infection and cancer cachexia: therapeutic intervention with N-acetylcysteine. Adv Pharmacol 1997; 38:581-600.
28. Ushmorov A, Hack V, Droge W. Differential reconstitution of mitochondrial respiratory chain activity and plasma redox state by cysteine and ornithine in a model of cancer cachexia. Cancer Res 1999; 59:3527-34. (Pubitemid 29334518)
29. Mantovani G, Maccio A, Madeddu C, Mulas C, Massa E, Astara G, et al. Phase II study of subcutaneously administered interleukin-2 in combination with medroxyprogesterone acetate and antioxidant agents as maintenance treatment in advanced cancer responders to previous chemotherapy. Oncol Rep 2002; 9:887-96.
30. Mantovani G, Maccio A, Madeddu C, Mura L, Gramignano G, Lusso MR, et al. Antioxidant agents are effective in inducing lymphocyte progression through cell cycle in advanced cancer patients: Assessment of the most important laboratory indexes of cachexia and oxidative stress. J Mol Med 2003; 81:664-73.
31. Mantovani G, Maccio A, Madeddu C, Mura L, Massa E, Gramignano G, et al. Reactive oxygen species, antioxidant mechanisms and serum cytokine levels in cancer patients: impact of an antioxidant treatment. J Cell Mol Med 2002; 6:570-82.
32. Mantovani G, Madeddu C, Gramignano G, Lusso MR, Mocci M, Massa E, et al. Subcutaneous interleukin-2 in combination with medroxyprogesterone acetate and antioxidants in advanced cancer responders to previous chemotherapy: phase II study evaluating clinical, quality of life and laboratory parameters. J Exp Ther Oncol 2003; 3:205-19.
33. Marin-Corral J, Fontes CC, Pascual-Guardia S, Sanchez F, Olivan M, Argiles JM, et al. Redox balance and carbonylated proteins in limb and heart muscles of cachectic rats. Antioxid Redox Signal 2010; 12:365-80.
34. Barreiro E, de la Puente B, Busquets S, Lopez-Soriano FJ, Gea J, Argiles JM. Both oxidative and nitrosative stress are associated with muscle wasting in tumour-bearing rats. FEBS Lett 2005; 579:1646-52. (Pubitemid 40341537)
35. Argiles JM. Cancer-associated malnutrition. Eur J Oncol Nurs 2005; 9:39-50.
36. Pennacchietti S, Michieli P, Galluzzo M, Mazzone M, Giordano S, Comoglio PM. Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell 2003; 3:347-61.
37. Steeg PS. Angiogenesis inhibitors: motivators of metastasis? Nat Med 2003; 9:822-3.
38. Grepin R, Pages G. Molecular mechanisms of resistance to tumour anti-angiogenic strategies. J Oncol 2010; 2010:835680.
39. Mancuso MR, Davis R, Norberg SM, O'Brien S, Sennino B, Nakahara T, et al. Rapid vascular regrowth in tumors after reversal of VEGF inhibition. J Clin Invest 2006; 116:2610-21.
40. Harris AL. Hypoxia - a key regulatory factor in tumour growth. Nat Rev Cancer 2002; 2:38-47.
41. Rapisarda A, Melillo G. Role of the hypoxic tumor microenvironment in the resistance to anti-angiogenic therapies. Drug Resist Updat 2009; 12:74-80.
42. Ide T, Kitajima Y, Miyoshi A, Ohtsuka T, Mitsuno M, Ohtaka K, et al. Tumor-stromal cell interaction under hypoxia increases the invasiveness of pancreatic cancer cells through the hepatocyte growth factor/c-Met pathway. Int J Cancer 2006; 119:2750-9.
43. Ebos JM, Lee CR, Cruz-Munoz W, Bjarnason GA, Christensen JG, Kerbel RS. Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell 2009; 15:232-9.
44. Erler JT, Bennewith KL, Cox TR, Lang G, Bird D, Koong A, et al. Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche. Cancer Cell 2009; 15:35-44.
45. Joyce JA, Pollard JW. Microenvironmental regulation of metastasis. Nat Rev Cancer 2009; 9:239-52.
46. Kerbel RS. Therapeutic implications of intrinsic or induced angiogenic growth factor redundancy in tumors revealed. Cancer Cell 2005; 8:269-71.
47. Casanovas O, Hicklin DJ, Bergers G, Hanahan D. Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell 2005; 8:299-309. (Pubitemid 41443415)
48. Peinado H, Cano A. A hypoxic twist in metastasis. Nat Cell Biol 2008; 10:253-4.
49. Yang MH, Wu MZ, Chiou SH, Chen PM, Chang SY, Liu CJ, et al. Direct regulation of TWIST by HIF-1alpha promotes metastasis. Nat Cell Biol 2008; 10:295-305.