Metabolites and the tumour microenvironment: from cellular mechanisms to systemic metabolism

被引:372
作者
Elia, Ilaria [1 ,2 ]
Haigis, Marcia C. [1 ,2 ]
机构
[1] Harvard Med Sch, Dept Cell Biol, Blavatnik Inst, Boston, MA 02115 USA
[2] Harvard Med Sch, Ludwig Canc Ctr, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
HUMAN PANCREATIC-CANCER; REGULATORY T-CELLS; AEROBIC GLYCOLYSIS; GLUTAMINE-METABOLISM; GENE-EXPRESSION; INDOLEAMINE 2,3-DIOXYGENASE; GLUCOSE DEPRIVATION; EFFECTOR FUNCTION; T-HELPER-1; CELL; IMMUNE CELLS;
D O I
10.1038/s42255-020-00317-z
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The tumour microenvironment (TME) is a unique cellular and metabolic landscape. Elia and Haigis describe how metabolism influences, and is affected by, the complexity of cellular interactions within the TME and highlight opportunities for therapeutic intervention. Metabolic transformation is a hallmark of cancer and a critical target for cancer therapy. Cancer metabolism and behaviour are regulated by cell-intrinsic factors as well as metabolite availability in the tumour microenvironment (TME). This metabolic niche within the TME is shaped by four tiers of regulation: (1) intrinsic tumour cell metabolism, (2) interactions between cancer cells and non-cancerous cells, (3) tumour location and heterogeneity and (4) whole-body metabolic homeostasis. Here, we define these modes of metabolic regulation and review how distinct cell types contribute to the metabolite composition of the TME. Finally, we connect these insights to understand how each of these tiers offers unique therapeutic potential to modulate the metabolic profile and function of all cells inhabiting the TME.
引用
收藏
页码:21 / 32
页数:12
相关论文
共 174 条
  • [1] Cell Culture Medium Formulation and Its Implications in Cancer Metabolism
    Ackermann, Tobias
    Tardito, Saverio
    [J]. TRENDS IN CANCER, 2019, 5 (06): : 329 - 332
  • [2] mTOR regulates memory CD8 T-cell differentiation
    Araki, Koichi
    Turner, Alexandra P.
    Shaffer, Virginia Oliva
    Gangappa, Shivaprakash
    Keller, Susanne A.
    Bachmann, Martin F.
    Larsen, Christian P.
    Ahmed, Rafi
    [J]. NATURE, 2009, 460 (7251) : 108 - U124
  • [3] A Stromal Lysolipid-Autotaxin Signaling Axis Promotes Pancreatic Tumor Progression
    Auciello, Francesca R.
    Bulusu, Vinay
    Oon, Chet
    Tat-Mulder, Jacqueline
    Berry, Mark
    Bhattacharyya, Sohinee
    Tumanov, Sergey
    Allen-Petersen, Brittany L.
    Link, Jason
    Kendsersky, Nicholas D.
    Vringer, Esmee
    Schug, Michelle
    Novo, David
    Hwang, Rosa F.
    Evans, Ronald M.
    Nixon, Colin
    Dorrell, Craig
    Morton, Jennifer P.
    Norman, Jim C.
    Sears, Rosalie C.
    Kamphorst, Jurre J.
    Sherman, Mara H.
    [J]. CANCER DISCOVERY, 2019, 9 (05) : 617 - 627
  • [4] Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells
    Battaglia, M
    Stabilini, A
    Roncarolo, MG
    [J]. BLOOD, 2005, 105 (12) : 4743 - 4748
  • [5] Rapamycin promotes expansion of functional CD4+CD25+FOXP3+ regulatory T cells of both healthy subjects and type 1 diabetic patients
    Battaglia, Manuela
    Stabilini, Angela
    Migliavacca, Barbara
    Horejs-Hoeck, Jutta
    Kaupper, Thomas
    Roncarolo, Maria-Grazia
    [J]. JOURNAL OF IMMUNOLOGY, 2006, 177 (12) : 8338 - 8347
  • [6] Tumor-Stroma Mechanics Coordinate Amino Acid Availability to Sustain Tumor Growth and Malignancy
    Bertero, Thomas
    Oldham, William M.
    Grasset, Eloise M.
    Bourget, Isabelle
    Boulter, Etienne
    Pisano, Sabrina
    Hofman, Paul
    Bellvert, Floriant
    Meneguzzi, Guerrino
    Bulavin, Dmitry, V
    Estrach, Soline
    Feral, Chloe C.
    Chan, Stephen Y.
    Bozec, Alexandre
    Gaggioli, Cedric
    [J]. CELL METABOLISM, 2019, 29 (01) : 124 - +
  • [7] An Essential Role of the Mitochondrial Electron Transport Chain in Cell Proliferation Is to Enable Aspartate Synthesis
    Birsoy, Kivanc
    Wang, Tim
    Chen, Walter W.
    Freinkman, Elizaveta
    Abu-Remaileh, Monther
    Sabatini, David M.
    [J]. CELL, 2015, 162 (03) : 540 - 551
  • [8] Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides
    Birsoy, Kivanc
    Possemato, Richard
    Lorbeer, Franziska K.
    Bayraktar, Erol C.
    Thiru, Prathapan
    Yucel, Burcu
    Wang, Tim
    Chen, Walter W.
    Clish, Clary B.
    Sabatini, David M.
    [J]. NATURE, 2014, 508 (7494) : 108 - +
  • [9] Cancer-Specific Loss of p53 Leads to a Modulation of Myeloid and T Cell Responses
    Blagih, Julianne
    Zani, Fabio
    Chakravarty, Probir
    Hennequart, Marc
    Pilley, Steven
    Hobor, Sebastijan
    Hock, Andreas K.
    Walton, Josephine B.
    Morton, Jennifer P.
    Gronroos, Eva
    Mason, Susan
    Yang, Ming
    McNeish, Iain
    Swanton, Charles
    Blyth, Karen
    Vousden, Karen H.
    [J]. CELL REPORTS, 2020, 30 (02): : 481 - +
  • [10] Amino acid levels determine metabolism and CYP450 function of hepatocytes and hepatoma cell lines
    Boon, Ruben
    Kumar, Manoj
    Tricot, Tine
    Elia, Ilaria
    Ordovas, Laura
    Jacobs, Frank
    One, Jennifer
    De Smedt, Jonathan
    Eelen, Guy
    Bird, Matthew
    Roelandt, Philip
    Doglioni, Ginevra
    Vriens, Kim
    Rossi, Matteo
    Vazquez, Marta Aguirre
    Vanwelden, Thomas
    Chesnais, Francois
    El Taghdouini, Adil
    Najimi, Mustapha
    Sokal, Etienne
    Cassiman, David
    Snoeys, Jan
    Monshouwer, Mario
    Hu, Wei-Shou
    Lange, Christian
    Carmeliet, Peter
    Fendt, Sarah-Maria
    Verfaillie, Catherine M.
    [J]. NATURE COMMUNICATIONS, 2020, 11 (01)