Glutamine and cancer.

Glutamine is the most abundant free amino acid in the human body; it is essential for the growth of normal and neoplastic cells and for the culture of many cell types. Cancer has been described as a nitrogen trap. The presence of a tumor produces great changes in host glutamine metabolism in such a way that host nitrogen metabolism is accommodated to the tumor-enhanced requirements of glutamine. To be used, glutamine must be transported into tumor mitochondria. Thus, an overview of the role of glutamine in cancer requires not only a discussion of host and tumor glutamine metabolism, but also its circulation and transport. Because glutamine depletion has adverse effects for the host, the effect of glutamine supplementation in the tumor-bearing state should also be studied. This communication reviews the state of knowledge of glutamine and cancer, including potential therapeutic implications.

[1]  B. Bode Recent molecular advances in mammalian glutamine transport. , 2001, The Journal of nutrition.

[2]  J. C. Aledo,et al.  Inhibition of glutaminase expression by antisense mRNA decreases growth and tumourigenicity of tumour cells. , 2000, The Biochemical journal.

[3]  J. Márquez,et al.  Changes in mRNAs for enzymes of glutamine metabolism in the tumor-bearing mouse. , 2000, Anticancer research.

[4]  rquez,et al.  Molecular cloning, sequencing and expression studies of the human breast cancer cell glutaminase. , 2000, The Biochemical journal.

[5]  D. Bell,et al.  The utility of tissue transglutaminase as a marker of apoptosis during treatment and progression of prostate cancer. , 1999, The Journal of urology.

[6]  R. Veltri,et al.  Human prostate-specific transglutaminase gene: promoter cloning, tissue-specific expression, and down-regulation in metastatic prostate cancer. , 1999, Urology.

[7]  M. Dewhirst,et al.  Tissue transglutaminase is expressed, active, and directly involved in rat dermal wound healing and angiogenesis , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[8]  W. Souba,et al.  Cloning and analysis of unique human glutaminase isoforms generated by tissue-specific alternative splicing. , 1999, Physiological genomics.

[9]  A. Miller Therapeutic considerations of L-glutamine: a review of the literature. , 1999, Alternative medicine review : a journal of clinical therapeutic.

[10]  Y. Cao,et al.  Glutamine protects against doxorubicin-induced cardiotoxicity. , 1999, The Journal of surgical research.

[11]  M. Medina,et al.  Glutamine, as a precursor of glutathione, and oxidative stress. , 1999, Molecular genetics and metabolism.

[12]  P. Schlag,et al.  Reduction of chemotherapy-induced side-effects by parenteral glutamine supplementation in patients with metastatic colorectal cancer. , 1999, European journal of cancer.

[13]  J. C. Aledo,et al.  Involvement of essential cysteine and histidine residues in the activity of isolated glutaminase from tumour cells. , 1998, Biochimica et biophysica acta.

[14]  J. Márquez,et al.  Early differential expression of two glutaminase mRNAs in mouse spleen after tumor implantation. , 1998, Cancer letters.

[15]  N. Verkaik,et al.  The human prostate-specific transglutaminase gene (TGM4): genomic organization, tissue-specific expression, and promoter characterization. , 1998, Genomics.

[16]  W. Souba,et al.  Regulation of glutamine synthetase in human breast carcinoma cells and experimental tumors. , 1997, Surgery.

[17]  F. Cappuzzo,et al.  Glutamine supplementation in cancer patients receiving chemotherapy: a double-blind randomized study. , 1997, Nutrition.

[18]  E. De Pedro,et al.  Submitochondrial localization and membrane topography of Ehrlich ascitic tumour cell glutaminase. , 1997, Biochimica et biophysica acta.

[19]  M. Dewhirst,et al.  Tissue transglutaminase expression in human breast cancer. , 1996, Laboratory investigation; a journal of technical methods and pathology.

[20]  V. Suzannec Klimberg,et al.  Glutamine, cancer, and its therapy* , 1996 .

[21]  Yves Agid,et al.  Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats , 1996, Nature Genetics.

[22]  M. Medina,et al.  Mobilization of glutamine and asparagine in mouse kidney during Ehrlich cell carcinoma development. , 1996, Cancer letters.

[23]  T. Kakegawa,et al.  Effect of glutamine supplementation on protein metabolism and glutathione in tumor-bearing rats. , 1995, JPEN. Journal of parenteral and enteral nutrition.

[24]  J. Márquez,et al.  Tumor glutaminase purification. , 1995, Protein expression and purification.

[25]  M. Medina,et al.  Glutamine transport by vesicles isolated from tumour-cell mitochondrial inner membrane. , 1995, The Biochemical journal.

[26]  J. Epstein,et al.  Glutamine Enhances Selectivity of Chemotherapy Through Changes in Glutathione Metabolism , 1995, Annals of surgery.

[27]  D. S. Lind,et al.  Normalization of Tumor‐Induced Increases in Hepatic Amino Acid Transport After Surgical Resection , 1995, Annals of surgery.

[28]  M. Fahr,et al.  Glutamine Enhances Immunoregulation of Tumor Growth , 1994 .

[29]  K. Mehta High levels of transglutaminase expression in doxorubicin‐resistant human breast carcinoma cells , 1994, International journal of cancer.

[30]  J. C. Aledo,et al.  Phosphate‐activated glutaminase expression during tumor development , 1994, FEBS letters.

[31]  W W Souba,et al.  Glutamine and Cancer , 1993, Annals of surgery.

[32]  K. Bland,et al.  The Effects of Glutamine‐enriched Total Parenteral Nutrition on Tumor Growth and Host Tissues , 1992, Annals of surgery.

[33]  M. Medina,et al.  l-Glutamine transport in native vesicles isolated from Ehrlich ascites tumor cell membranes , 1991, Journal of bioenergetics and biomembranes.

[34]  J. Márquez,et al.  Mouse liver free amino acids during the development of Ehrlich ascites tumour. , 1991, Cancer letters.

[35]  F. Sánchez-Jiménez,et al.  Glycolysis and glutaminolysis in perifused ehrlich ascites tumour cells , 1989, Cell biochemistry and function.

[36]  F. Sánchez-Jiménez,et al.  Purification of phosphate-dependent glutaminase from isolated mitochondria of Ehrlich ascites-tumour cells. , 1988, The Biochemical journal.

[37]  M. Medina,et al.  Evidence of an Intracellular Dissipative Structure , 1988, Zeitschrift fur Naturforschung. C, Journal of biosciences.

[38]  F. Marquez,et al.  Effect of palmitate, acetate and glucose on glutamine metabolism in Ehrlich ascites tumor cells. , 1988, Biochimie.

[39]  F. Marquez,et al.  Inorganic phosphate and energy charge compartmentation in Ehrlich ascites tumour cells in the presence of glucose and/or glutamine. , 1988, Biochemistry international.

[40]  F. Sánchez-Jiménez,et al.  Contribution by host tissues to circulating glutamine in mice inoculated with Ehrlich ascites tumor cells. , 1988, Cancer research.

[41]  S. Ji,et al.  The bhopalator: a molecular model of the living cell based on the concepts of conformons and dissipative structures. , 1985, Journal of theoretical biology.

[42]  I. Núñez de Castro,et al.  Nitrogen movement between host and tumor in mice inoculated with Ehrlich ascitic tumor cells. , 1984, Cancer research.

[43]  Z. Kovačević,et al.  Conditions for activity of glutaminase in kidney mitochondria. , 1970, The Biochemical journal.

[44]  G. Mider Some aspects of nitrogen and energy metabolism in cancerous subjects: a review. , 1951, Cancer research.

[45]  S. Park,et al.  Reduction of transglutaminase 2 expression is associated with an induction of drug sensitivity in the PC-14 human lung cancer cell line , 1999, Journal of Cancer Research and Clinical Oncology.

[46]  M. Medina,et al.  Glutaminolysis and glycolysis interactions in proliferant cells. , 1990, The International journal of biochemistry.

[47]  W. Hammond,et al.  Aspects of amino acid and protein metabolism in cancer‐bearing states , 1985, Cancer.

[48]  B. Crabtree,et al.  A quantitative approach to metabolic control. , 1985, Current topics in cellular regulation.

[49]  V. Shapot On the multiform relationships between the tumor and the host. , 1979, Advances in cancer research.

[50]  Knox We,et al.  A comparative study of glytaminase isozymes in rat tissues. , 1976 .