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Cancer Development in Competitive and Hostile Environments

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Cancer Bioinformatics

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Abstract

From the perspective of cancer cells, they reside and must survive in a highly stressful and unfriendly environment. From the beginning, the cells have been under tremendous pressure to evolve in order to rid themselves of accumulated glucose metabolites and hence survival via cell division, as discussed in Chap. 5. In order to sustain their proliferation for long-term survival, they must continuously adjust their metabolism to adapt to the micro-environmental stresses and concurrently avoid the detection and destruction by myriad defense mechanisms that are present in humans to neutralize and destroy infectious organisms and aberrant cells. The adaptations of these cells to the challenging environment continue to drive their metabolism to become increasingly more irregular. As they continue to accumulate abnormalities, these cells must also continue to evolve to gain additional protection, thus ensuring their survival in the increasingly hostile environment. The ongoing processes of evolution and adaptation may drive the cellular metabolism to become even more anomalous, thus forming a vicious cycle and serving as a new driver for survival via proliferation. The defense systems that these evolving cells must overcome include: (1) the cellular surveillance and protection systems such as apoptosis and limited growth potential; (2) competition from the neighboring cells, a tissue-level mechanism for eliminating less fit cells and (3) the immune system. The main question addressed in this chapter is: How have the cancer cells evolved to survive these obstacles and become increasingly more malignant? The question of how the cancer cells respond to and overcome other microenvironment-induced stresses will be deferred to Chap. 9.

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References

  • Alberts B, Johnson A, Lewis J et al. (2002) Molecular Biology of the Cell. 4th edn. New York and London: Garland Science,

    Google Scholar 

  • Arnold SA, Brekken RA (2009) SPARC: a matricellular regulator of tumorigenesis. Journal of cell communication and signaling 3: 255-273

    Article  Google Scholar 

  • Baker NE (2011) Cell competition. Current Biology 21: R11-R15

    Article  Google Scholar 

  • Balmanno K, Cook SJ (2009) Tumour cell survival signalling by the ERK1/2 pathway. Cell death and differentiation 16: 368-377

    Article  Google Scholar 

  • Bingle L, Brown NJ, Lewis CE (2002) The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol 196: 254-265

    Article  Google Scholar 

  • Bondar T, Medzhitov R (2010a) p53-mediated hematopoietic stem and progenitor cell competition. Cell stem cell 6: 309-322

    Article  Google Scholar 

  • Bondar T, Medzhitov R (2010b) p53-mediated hematopoietic stem and progenitor cell competition. Cell Stem Cell 6: 309-322

    Article  Google Scholar 

  • Burchard J, Zhang C, Liu AM et al. (2010) microRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma. Mol Syst Biol 6: 402

    Google Scholar 

  • Calorini L, Peppicelli S, Bianchini F (2012) Extracellular acidity as favouring factor of tumor progression and metastatic dissemination. Experimental oncology 34: 79-84

    Google Scholar 

  • Casey JR, Grinstein S, Orlowski J (2010) Sensors and regulators of intracellular pH. Nat Rev Mol Cell Biol 11: 50-61

    Article  Google Scholar 

  • Chandran UR, Ma C, Dhir R et al. (2007) Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process. BMC Cancer 7: 64

    Article  Google Scholar 

  • Charles AJP, T.; Mark, W.; Mark, J.S. (2001) Immunobiology: The Immune System in Health and Disease. 5th edn. New York: Garland Science,

    Google Scholar 

  • Chiche J, Brahimi-Horn MC, Pouyssegur J (2010) Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer. J Cell Mol Med 14: 771-794

    Article  Google Scholar 

  • Cotter PD, Hill C (2003) Surviving the acid test: responses of gram-positive bacteria to low pH. Microbiol Mol Biol Rev 67: 429-453, table of contents

    Google Scholar 

  • de la Cova C, Abril M, Bellosta P et al. (2004) Drosophila Myc Regulates Organ Size by Inducing Cell Competition. Cell 117: 107-116

    Article  Google Scholar 

  • de Visser KE, Eichten A, Coussens LM (2006) Paradoxical roles of the immune system during cancer development. Nature reviews Cancer 6: 24-37

    Article  Google Scholar 

  • DeBerardinis RJ, Lum JJ, Hatzivassiliou G et al. (2008) The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 7: 11-20

    Article  Google Scholar 

  • Dighe AS, Richards E, Old LJ et al. (1994) Enhanced in vivo growth and resistance to rejection of tumor cells expressing dominant negative IFN gamma receptors. Immunity 1: 447-456

    Article  Google Scholar 

  • Dirkx AE, Oude Egbrink MG, Wagstaff J et al. (2006) Monocyte/macrophage infiltration in tumors: modulators of angiogenesis. J Leukoc Biol 80: 1183-1196

    Article  Google Scholar 

  • Donowitz M, Li X (2007) Regulatory binding partners and complexes of NHE3. Physiol Rev 87: 825-872

    Article  Google Scholar 

  • Dunn GP, Bruce AT, Ikeda H et al. (2002) Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 3: 991-998

    Article  Google Scholar 

  • Edgar R, Domrachev M, Lash AE (2002) Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res 30: 207-210

    Article  Google Scholar 

  • Fischer K, Hoffmann P, Voelkl S et al. (2007) Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood 109: 3812-3819

    Article  Google Scholar 

  • Ganapathy V, Thangaraju M, Prasad PD (2009) Nutrient transporters in cancer: relevance to Warburg hypothesis and beyond. Pharmacol Ther 121: 29-40

    Article  Google Scholar 

  • Goretzki L, Schmitt M, Mann K et al. (1992) Effective activation of the proenzyme form of the urokinase-type plasminogen activator (pro-uPA) by the cysteine protease cathepsin L. FEBS Lett 297: 112-118

    Article  Google Scholar 

  • Gross A, McDonnell JM, Korsmeyer SJ (1999) BCL-2 family members and the mitochondria in apoptosis. Genes & development 13: 1899-1911

    Article  Google Scholar 

  • Halestrap AP (2012) The monocarboxylate transporter family–Structure and functional characterization. IUBMB Life 64: 1-9

    Article  Google Scholar 

  • Halestrap AP, Price NT (1999) The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation. Biochem J 343 Pt 2: 281-299

    Article  Google Scholar 

  • Hamel K, Doodes P, Cao Y et al. (2008) Suppression of Proteoglycan-Induced Arthritis by Anti-CD20 B Cell Depletion Therapy Is Mediated by Reduction in Autoantibodies and CD4+ T Cell Reactivity. The Journal of Immunology 180: 4994-5003

    Article  Google Scholar 

  • Hinoue T, Weisenberger DJ, Lange CP et al. (2012) Genome-scale analysis of aberrant DNA methylation in colorectal cancer. Genome Res 22: 271-282

    Article  Google Scholar 

  • Hirschhaeuser F, Sattler UG, Mueller-Klieser W (2011) Lactate: a metabolic key player in cancer. Cancer research 71: 6921-6925

    Article  Google Scholar 

  • Houghton AN, Guevara-Patino JA (2004) Immune recognition of self in immunity against cancer. The Journal of clinical investigation 114: 468-471

    Article  Google Scholar 

  • Hudson TJ, Anderson W, Artez A et al. (2010) International network of cancer genome projects. Nature 464: 993-998

    Article  Google Scholar 

  • Husain Z, Huang Y, Seth P et al. (2013) Tumor-derived lactate modifies antitumor immune response: effect on myeloid-derived suppressor cells and NK cells. Journal of immunology 191: 1486-1495

    Article  Google Scholar 

  • Hyde TM, Lipska BK, Ali T et al. (2011) Expression of GABA signaling molecules KCC2, NKCC1, and GAD1 in cortical development and schizophrenia. J Neurosci 31: 11088-11095

    Article  Google Scholar 

  • Itel F, Al-Samir S, Oberg F et al. (2012) CO2 permeability of cell membranes is regulated by membrane cholesterol and protein gas channels. FASEB J 26: 5182-5191

    Article  Google Scholar 

  • Johnson DE, Casey JR (2009) Bicarbonate Transport Metabolons. In: Supuran CT, Winum JY (eds) Drug Design of Zinc-Enzyme Inhibitors: Functional, Structural, and Disease Applications. Wiley, Hoboken, New Jersey, pp 415–437

    Chapter  Google Scholar 

  • Johnston LA (2009) Competitive interactions between cells: death, growth, and geography. Science 324: 1679-1682

    Article  Google Scholar 

  • Kim R, Emi M, Tanabe K (2007) Cancer immunoediting from immune surveillance to immune escape. Immunology 121: 1-14

    Article  Google Scholar 

  • Levayer R, Moreno E (2013) Mechanisms of cell competition: themes and variations. The Journal of cell biology 200: 689-698

    Article  Google Scholar 

  • Liu Y, Zuckier L, Ghesani N (2008) Fatty acid rather than glucose metabolism is the dominant bioenergetic pathway in prostate cancer. J NUCL MED MEETING ABSTRACTS 49: 104P-a-

    Google Scholar 

  • Lu P, Weaver VM, Werb Z (2012) The extracellular matrix: a dynamic niche in cancer progression. The Journal of cell biology 196: 395-406

    Article  Google Scholar 

  • MacKie RM, Reid R, Junor B (2003) Fatal melanoma transferred in a donated kidney 16 years after melanoma surgery. N Engl J Med 348: 567-568

    Article  Google Scholar 

  • Mahnensmith RL, Aronson PS (1985) The plasma membrane sodium-hydrogen exchanger and its role in physiological and pathophysiological processes. Circulation research 56: 773-788

    Article  Google Scholar 

  • Matsuyama T, Ishikawa T, Mogushi K et al. (2010) MUC12 mRNA expression is an independent marker of prognosis in stage II and stage III colorectal cancer. Int J Cancer 127: 2292-2299

    Article  Google Scholar 

  • Mok SC, Chan WY, Wong KK et al. (1996) SPARC, an extracellular matrix protein with tumor-suppressing activity in human ovarian epithelial cells. Oncogene 12: 1895-1901

    Google Scholar 

  • Moreno E, Basler K (2004) dMyc Transforms Cells into Super-Competitors. Cell 117: 117-129

    Article  Google Scholar 

  • Nagase H, Visse R, Murphy G (2006) Structure and function of matrix metalloproteinases and TIMPs. Cardiovascular Research 69: 562-573

    Article  Google Scholar 

  • The Cancer Genome Atlas Data Portal (2010).

    Google Scholar 

  • Neto-Silva RM, de Beco S, Johnston LA (2010) Evidence for a Growth-Stabilizing Regulatory Feedback Mechanism between Myc and Yorkie, the Drosophila Homolog of Yap. Developmental cell 19: 507-520

    Article  Google Scholar 

  • Nishi H, Nakada T, Kyo S et al. (2004) Hypoxia-inducible factor 1 mediates upregulation of telomerase (hTERT). Molecular and cellular biology 24: 6076-6083

    Article  Google Scholar 

  • Pau Ni IB, Zakaria Z, Muhammad R et al. (2010) Gene expression patterns distinguish breast carcinomas from normal breast tissues: the Malaysian context. Pathol Res Pract 206: 223-228

    Article  Google Scholar 

  • Pena-Llopis S, Vega-Rubin-de-Celis S, Schwartz JC et al. (2011) Regulation of TFEB and V-ATPases by mTORC1. The EMBO journal 30: 3242-3258

    Article  Google Scholar 

  • Perez-Sayans M, Somoza-Martin JM, Barros-Angueira F et al. (2009) V-ATPase inhibitors and implication in cancer treatment. Cancer Treat Rev 35: 707-713

    Article  Google Scholar 

  • Petrova E, Lopez-Gay JM, Rhiner C et al. (2012) Flower-deficient mice have reduced susceptibility to skin papilloma formation. Disease models & mechanisms 5: 553-561

    Article  Google Scholar 

  • Pinheiro C, Reis RM, Ricardo S et al. (2010) Expression of monocarboxylate transporters 1, 2, and 4 in human tumours and their association with CD147 and CD44. J Biomed Biotechnol 2010: 427694

    Article  Google Scholar 

  • Portela M, Casas-Tinto S, Rhiner C et al. (2010) Drosophila SPARC is a self-protective signal expressed by loser cells during cell competition. Developmental cell 19: 562-573

    Article  Google Scholar 

  • Prober DA, Edgar BA (2000) Ras1 Promotes Cellular Growth in the < i > Drosophila</i > Wing. Cell 100: 435-446

    Article  Google Scholar 

  • Proescholdt MA, Mayer C, Kubitza M et al. (2005) Expression of hypoxia-inducible carbonic anhydrases in brain tumors. Neuro Oncol 7: 465-475

    Article  Google Scholar 

  • Puolakkainen PA, Brekken RA, Muneer S et al. (2004) Enhanced growth of pancreatic tumors in SPARC-null mice is associated with decreased deposition of extracellular matrix and reduced tumor cell apoptosis. Molecular cancer research : MCR 2: 215-224

    Google Scholar 

  • Rhiner C, Lopez-Gay JM, Soldini D et al. (2010) Flower forms an extracellular code that reveals the fitness of a cell to its neighbors in Drosophila. Developmental cell 18: 985-998

    Article  Google Scholar 

  • Riemann A, Schneider B, Ihling A et al. (2011) Acidic environment leads to ROS-induced MAPK signaling in cancer cells. PloS one 6: e22445

    Article  Google Scholar 

  • Rosenbloom KR, Dreszer TR, Long JC et al. (2012) ENCODE whole-genome data in the UCSC Genome Browser: update 2012. Nucleic Acids Res 40: D912-917

    Article  Google Scholar 

  • Rozhin J, Sameni M, Ziegler G et al. (1994) Pericellular pH affects distribution and secretion of cathepsin B in malignant cells. Cancer research 54: 6517-6525

    Google Scholar 

  • Ruvolo P, Deng X, May W (2001) Phosphorylation of Bcl2 and regulation of apoptosis. Leukemia (08876924) 15:

    Google Scholar 

  • Ryder C, McColl K, Zhong F et al. (2012a) Acidosis promotes Bcl-2 family-mediated evasion of apoptosis: involvement of acid-sensing G protein-coupled receptor Gpr65 signaling to Mek/Erk. The Journal of biological chemistry 287: 27863-27875

    Article  Google Scholar 

  • Ryder C, McColl K, Zhong F et al. (2012b) Acidosis Promotes Bcl-2 Family-mediated Evasion of Apoptosis: INVOLVEMENT OF ACID-SENSING G PROTEIN-COUPLED RECEPTOR GPR65 SIGNALING TO MEK/ERK. Journal of Biological Chemistry 287: 27863-27875

    Article  Google Scholar 

  • Sansom OJ, Mansergh FC, Evans MJ et al. (2007) Deficiency of SPARC suppresses intestinal tumorigenesis in APCMin/+mice. Gut 56: 1410-1414

    Article  Google Scholar 

  • Simpson P (1979) Parameters of cell competition in the compartments of the wing disc of Drosophila. Developmental biology 69: 182-193

    Article  Google Scholar 

  • Simpson P, Morata G (1981) Differential mitotic rates and patterns of growth in compartments in the Drosophila wing. Developmental biology 85: 299-308

    Article  Google Scholar 

  • Slomiany MG, Grass GD, Robertson AD et al. (2009) Hyaluronan, CD44, and emmprin regulate lactate efflux and membrane localization of monocarboxylate transporters in human breast carcinoma cells. Cancer research 69: 1293-1301

    Article  Google Scholar 

  • Sorokin L (2010) The impact of the extracellular matrix on inflammation. Nature reviews Immunology 10: 712-723

    Article  Google Scholar 

  • Su LJ, Chang CW, Wu YC et al. (2007) Selection of DDX5 as a novel internal control for Q-RT-PCR from microarray data using a block bootstrap re-sampling scheme. BMC Genomics 8: 140

    Article  Google Scholar 

  • Swietach P, Vaughan-Jones RD, Harris AL (2007) Regulation of tumor pH and the role of carbonic anhydrase 9. Cancer Metastasis Rev 26: 299-310

    Article  Google Scholar 

  • Tamori Y, Deng WM (2011) Cell competition and its implications for development and cancer. Journal of genetics and genomics = Yi chuan xue bao 38: 483-495

    Article  Google Scholar 

  • Tan XL, Marquardt G, Massimi AB et al. (2012) High-throughput library screening identifies two novel NQO1 inducers in human lung cells. Am J Respir Cell Mol Biol 46: 365-371

    Article  Google Scholar 

  • Taraboletti G, D’Ascenzo S, Giusti I et al. (2006) Bioavailability of VEGF in tumor-shed vesicles depends on vesicle burst induced by acidic pH. Neoplasia 8: 96-103

    Article  Google Scholar 

  • Taylor BS, Schultz N, Hieronymus H et al. (2010) Integrative genomic profiling of human prostate cancer. Cancer Cell 18: 11-22

    Article  Google Scholar 

  • Thomas L (1982) On immunosurveillance in human cancer. Yale J Biol Med 55: 329-333

    Google Scholar 

  • Trachootham D, Alexandre J, Huang P (2009) Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nature reviews Drug discovery 8: 579-591

    Article  Google Scholar 

  • Tung EK, Mak CK, Fatima S et al. (2011) Clinicopathological and prognostic significance of serum and tissue Dickkopf-1 levels in human hepatocellular carcinoma. Liver Int 31: 1494-1504

    Article  Google Scholar 

  • Uva P, Aurisicchio L, Watters J et al. (2009) Comparative expression pathway analysis of human and canine mammary tumors. BMC Genomics 10: 135

    Article  Google Scholar 

  • Vivarelli S, Wagstaff L, Piddini E (2012) Cell wars: regulation of cell survival and proliferation by cell competition. Essays Biochem 53: 69-82

    Article  Google Scholar 

  • Wang HW, Joyce JA (2010) Alternative activation of tumor-associated macrophages by IL-4: priming for protumoral functions. Cell cycle 9: 4824-4835

    Article  Google Scholar 

  • Wang YY, Wu SX, Liu XY et al. (2003) Effects of c-fos antisense oligodeoxynucleotide on 5-HT-induced upregulation of preprodynorphin, preproenkephalin, and glutamic acid decarboxylase mRNA expression in cultured rat spinal dorsal horn neurons. Biochem Biophys Res Commun 309: 631-636

    Article  Google Scholar 

  • Wu H, Ding Z, Hu D et al. (2012) Central role of lactic acidosis in cancer cell resistance to glucose deprivation-induced cell death. J Pathol 227: 189-199

    Article  Google Scholar 

  • Xu K, Mao X, Mehta M et al. (2013) Elucidation of how cancer cells avoid acidosis through comparative transcriptomic data analysis. PloS one 8: e71177

    Article  Google Scholar 

  • Yao CK, Lin YQ, Ly CV et al. (2009) A synaptic vesicle-associated Ca2+ channel promotes endocytosis and couples exocytosis to endocytosis. Cell 138: 947-960

    Article  Google Scholar 

  • Yusuf N, Nasti TH, Katiyar SK et al. (2008) Antagonistic roles of CD4+ and CD8+ T-cells in 7,12-dimethylbenz(a)anthracene cutaneous carcinogenesis. Cancer research 68: 3924-3930

    Article  Google Scholar 

  • Zambelli F, Prazzoli GM, Pesole G et al. (2012) Cscan: finding common regulators of a set of genes by using a collection of genome-wide ChIP-seq datasets. Nucleic Acids Res 40: W510-515

    Article  Google Scholar 

  • Ziosi M, Baena-Lopez LA, Grifoni D et al. (2010) dMyc functions downstream of Yorkie to promote the supercompetitive behavior of hippo pathway mutant cells. PLoS genetics 6: e1001140

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, USA

    Ying Xu & David Puett

  2. Department of Computer Science and Engineering, University of Nebraska, Lincoln, NE, USA

    Juan Cui

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  1. Ying Xu
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Appendix

Appendix

The gene-expression data for the six cancer types, (breast, colon, liver, lung adenocarcinoma, squamous cell lung, prostate), were downloaded from the GEO database (Edgar et al. 2002) of the NCBI. For each cancer type, the following criteria were applied in selecting the dataset used for this study: (1) all the data in each dataset were generated using the same platform by the same research group; (2) each dataset consists of only paired samples, i.e., cancer tissue sample and the matching adjacent noncancerous tissue sample; and (3) each dataset has at least ten pairs of samples. In the GEO database, only six cancer types have datasets satisfying these criteria. A summary of the 12 datasets, 2 sets for each cancer, is listed in the following table.

Table 8.1 Gene expression data for six cancer types used in transcriptomic data analysis in Sect. 8.2
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Xu, Y., Cui, J., Puett, D. (2014). Cancer Development in Competitive and Hostile Environments. In: Cancer Bioinformatics. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1381-7_8

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