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Lactate is a mediator of metabolic cooperation between stromal carcinoma associated fibroblasts and glycolytic tumor cells in the tumor microenvironment
Open accessAbstract
Human mesenchymal stem cells (hMSCs) are bone marrow-derived stromal cells, which play a role in tumor progression. We have shown earlier that breast cancer cells secrete higher levels of interleukin-6 (IL-6) under hypoxia, leading to the recruitment of hMSCs towards hypoxic tumor cells. We found that (i) MDA-MB-231 cells secrete significantly higher levels of lactate (3-fold more) under hypoxia (1% O(2)) than under 20% O(2) and (ii) lactate recruits hMSCs towards tumor cells by activating signaling pathways to enhance migration. The mRNA and protein expression of functional MCT1 in hMSCs is increased in response to lactate exposure. Thus, we hypothesized that hMSCs and stromal carcinoma associated fibroblasts (CAFs) in the tumor microenvironment have the capacity to take up lactate expelled from tumor cells and use it as a source of energy. Our (13)C NMR spectroscopic measurements indicate that (13)C-lactate is converted to (13)C-alpha ketoglutarate in hMSCs and CAFs supporting this hypothesis. To our knowledge this is the first in vitro model system demonstrating that hMSCs and CAFs can utilize lactate produced by tumor cells.
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“Recent findings implicate TME in the induced metabolic rewiring in cancer cells (Cairns et al., 2011; Fiaschi and Chiarugi, 2012; Rattigan et al., 2012).”
From Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism (2016) · cites this paper as Rattigan et al., 2012
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Cites
Warburg, O. (1956) · Science · doi:10.1126/science.123.3191.309 · Cited by 13,425
Why Do Cancers Have High Aerobic Glycolysis?
Gatenby, R. A., & Gillies, R. J. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1478 · Cited by 4,784
On Respiratory Impairment in Cancer Cells
Warburg, O. H. (1956) · Science · doi:10.1126/science.124.3215.269 · Cited by 3,472
Cancer cell metabolism: warburg and beyond
Hsu, P. P., & Sabatini, D. M. (2008) · Cell · doi:10.1016/j.cell.2008.08.021 · Cited by 2,452 · cited 1×
“Further, tumor-secreted lactate has been suggested to act as a paracrine molecule to affect signaling in the neighboring stroma [40].”
Tumor cell metabolism: cancer's Achilles' heel
Kroemer, G., & Pouyssegur, J. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.05.005 · Cited by 2,337
Inhibitory effect of tumor cell-derived lactic acid on human T cells
Fischer, K., Hoffmann, P., Voelkl, S., Meidenbauer, N., Ammer, J., Edinger, M., Gottfried, E., Schwarz, S., Rothe, G., Hoves, S., et al. (2007) · Blood · doi:10.1182/blood-2006-07-035972 · Cited by 1,946
Helmlinger, G., Yuan, F., Dellian, M., & Jain, R. K. (1997) · Nature Medicine · doi:10.1038/nm0297-177 · Cited by 1,651
(1989) · PubMed · Cited by 1,639
Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice
Sonveaux, P., Végran, F., Schroeder, T., Wergin, M., Verrax, J., Rabbani, Z. N., Saedeleer, C. J. D., Kennedy, K. M., Diepart, C., Jordan, B. F., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci36843 · Cited by 1,635
Fantin, V. R., St-Pierre, J., & Leder, P. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.04.023 · Cited by 1,635
The reverse Warburg effect: Aerobic glycolysis in cancer associated fibroblasts and the tumor stroma
Pavlides, S., Whitaker-Menezes, D., Castello-Cros, R., Flomenberg, N., Witkiewicz, A. K., Frank, P. G., Casimiro, M. C., Wang, C., Fortina, P., Addya, S., et al. (2009) · Cell Cycle · doi:10.4161/cc.8.23.10238 · Cited by 1,391
The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation
Halestrap, A. P., & Price, N. T. (1999) · Biochemical Journal · doi:10.1042/bj3430281 · Cited by 1,346
Lactate metabolism: a new paradigm for the third millennium
Gladden, L. B. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2003.058701 · Cited by 1,332
Oncogenic alterations of metabolism
Dang, C. V., & Semenza, G. L. (1999) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(98)01344-9 · Cited by 1,106
Halestrap, A. P., & Meredith, D. (2004) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-003-1067-2 · Cited by 1,047
Brick by brick: metabolism and tumor cell growth
DeBerardinis, R. J., Sayed, N., Ditsworth, D., & Thompson, C. B. (2008) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2008.02.003 · Cited by 1,018
Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells
Mishra, P. J., Mishra, P. J., Humeniuk, R., Medina, D. J., Alexe, G., Mesirov, J. P., Ganesan, S., Glod, J. W., & Banerjee, D. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-0943 · Cited by 912
Self-citationFeron, O. (2009) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2009.06.025 · Cited by 559
Tomchuck, S. L., Zwezdaryk, K. J., Coffelt, S. B., Waterman, R. S., Danka, E. S., & Scandurro, A. B. (2007) · Stem Cells · doi:10.1634/stemcells.2007-0563 · Cited by 449
Hashimoto, T., Hussien, R., Oommen, S., Gohil, K., & Brooks, G. A. (2007) · The FASEB Journal · doi:10.1096/fj.07-8174com · Cited by 442
Koukourakis, M. I., Giatromanolaki, A. N., Harris, A. L., & Sivridis, E. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-3260 · Cited by 438
Brooks, G. A. (2002) · Biochemical Society Transactions · doi:10.1042/bst0300258 · Cited by 429
Lactic Acid and Acidification Inhibit TNF Secretion and Glycolysis of Human Monocytes
Dietl, K., Renner, K., Dettmer, K., Timischl, B., Eberhart, K., Dorn, C., Hellerbrand, C., Kastenberger, M., Kunz‐Schughart, L. A., Oefner, P. J., et al. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0902584 · Cited by 402
Lactate and energy metabolism in male germ cells
Boussouar, F., & Benahmed, M. (2004) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2004.07.003 · Cited by 355
Samudio, I. J., Fiegl, M., & Andreeff, M. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-3722 · Cited by 309
Ackerstaff, E., Pflug, B. R., Nelson, J. B., & Bhujwalla, Z. M. (2001) · PubMed · Cited by 285
Self-citationSamuvel, D. J., Sundararaj, K. P., Nareika, A., Lopes-Virella, M. F., & Huang, Y. Q. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0802059 · Cited by 223
Adaptive landscapes and emergent phenotypes: why do cancers have high glycolysis?
Gillies, R. J., & Gatenby, R. A. (2007) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-007-9085-y · Cited by 219
Koukourakis, M. I., Giatromanolaki, A., Sivridis, E., Gatter, K. C., & Harris, A. L. (2005) · Neoplasia · doi:10.1593/neo.04373 · Cited by 214
Gao, H., Priebe, W., Glod, J. W., & Banerjee, D. (2009) · Stem Cells · doi:10.1002/stem.23 · Cited by 202
Self-citationInduction of Oxidative Metabolism by Mitochondrial Frataxin Inhibits Cancer Growth
Schulz, T. J., Thierbach, R., Voigt, A., Drewes, G., Mietzner, B., Steinberg, P., Pfeiffer, A. F. H., & Ristow, M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m511064200 · Cited by 198
DelaRosa, O., & Lombardo, E. (2010) · Mediators of Inflammation · doi:10.1155/2010/865601 · Cited by 197
Mangia, S., Simpson, I. A., Vannucci, S. J., & Carruthers, A. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06003.x · Cited by 189
Interleukin 6 mediated recruitment of mesenchymal stem cells to the hypoxic tumor milieu
Rattigan, Y. I., Hsu, J., Mishra, P. J., Glod, J. W., & Banerjee, D. (2010) · Experimental Cell Research · doi:10.1016/j.yexcr.2010.07.002 · Cited by 183
Self-citationFang, J., Quiñones, Q. J., Holman, T. L., Morowitz, M. J., Wang, Q., Zhao, H., Sivo, F., Maris, J. M., & Wahl, M. (2006) · Molecular Pharmacology · doi:10.1124/mol.106.026245 · Cited by 171
Samudio, I., Fiegl, M., McQueen, T., Clise-Dwyer, K., & Andreeff, M. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-0555 · Cited by 168
Mathupala, S. P., Parajuli, P., & Sloan, A. E. (2004) · Neurosurgery · doi:10.1227/01.neu.0000143034.62913.59 · Cited by 147
Slomiany, M. G., Grass, G. D., Robertson, A. D., Xiao, Y., Maria, B. L., Beeson, C. C., & Toole, B. P. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-2491 · Cited by 144
Oxidative metabolism in cancer growth
Ristow, M. (2006) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/01.mco.0000232892.43921.98 · Cited by 132
Lung cancer: An organized cellular and metabolic domain
Koukourakis, M. I., Giatromanolaki, A. N., Bougioukas, G., & Sivridis, E. (2007) · Cancer Biology & Therapy · doi:10.4161/cbt.6.9.4635 · Cited by 100
Cancer’s craving for sugar: an opportunity for clinical exploitation
Yeluri, S., Madhok, B., Prasad, R. K., Quirke, P., & Jayne, D. G. (2009) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-009-0590-8 · Cited by 58
Tumor Microenvironment Modulates Hyaluronan Expression: The Lactate Effect
Rudrabhatla, S. R., Mahaffey, C. L., & Mummert, M. E. (2006) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700255 · Cited by 44
Street, J. C., Mahmood, U., Ballon, D., Alfieri, A. A., & Koutcher, J. A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.8.4113 · Cited by 35
Self-citationViswanathan, T. S., Johnson, R. E., & Fisher, H. F. (1982) · Biochemistry · doi:10.1021/bi00531a022 · Cited by 27
Martin, G., Chauvin, M.-F., Dugelay, S., & Baverel, G. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47155-4 · Cited by 21
Research works printed but not linked: 2
- Samuvel, 2009, Lactate boosts TLR4 signaling and NF-kappaB pathway-mediated gene transcription in macrophages via monocarboxylate transporters and MD-2 up-regulation, J. Immunol., 182, 2476, 10.4049/jimmunol.0802059 · DOI
- Koukourakis, 2007, Lung cancer: a comparative study of metabolism related protein expression in cancer cells and tumor associated stroma, Cancer Biol. Ther., 6, 1476
Cited by
Sorted by citations
Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment
Hanahan, D., & Coussens, L. M. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.02.022 · Cited by 4,632
Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism
Zhao, H., Yang, L., Baddour, J., Achreja, A., Bernard, V., Moss, T., Marini, J. C., Tudawe, T., Seviour, E. G., San Lucas, F. A., et al. (2016) · eLife · doi:10.7554/elife.10250 · Cited by 927
Metabolic Interactions in the Tumor Microenvironment
Lyssiotis, C. A., & Kimmelman, A. C. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.06.003 · Cited by 853
“For example, breast and colon cancer cells consume glucose and release lactate to surrounding fibroblasts and mesenchymal stem cells [56, 57] (Fig.”
BackgroundHusain, Z., Huang, Y., Seth, P., & Sukhatme, V. P. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1202702 · Cited by 827
Fiaschi, T., Marini, A., Giannoni, E., Taddei, M. L., Gandellini, P., Donatis, A. D., Lanciotti, M., Serni, S., Cirri, P., & Chiarugi, P. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-1949 · Cited by 598
Metadata
- Authors
- Rattigan, Y. I., Patel, B. B., Ackerstaff, E., Sukenick, G., Koutcher, J. A., Glod, J. W., & Banerjee, D.
- Affiliations
- Rutgers Cancer Institute (US)
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Banerjee, Debabrata
- Venue
- Experimental Cell Research
- Publisher
- Elsevier BV
- Published
- 2012-02
- Volume
- 318
- Issue
- 4
- Pages
- 326-335
- ISSN
- 0014-4827 (ISSN-L)
- PMC
- PMC3402174
- OpenAlex
- W2106506721
- Cited by
- 196
- References
- 46
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 27 · 2023: 16 · 2022: 13 · 2021: 15 · 2020: 20 · 2019: 10 · 2018: 9 · 2017: 16 · 2016: 11 · 2015: 15 · 2014: 12 · 2013: 9 · 2012: 6
- FWCI
- 2.94
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Experimental Cell Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (CA83084, P01 CA94060)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- lactate, metabolic cooperation, human mesenchymal stem cells, tumor microenvironment, hypoxia, breast cancer, MDA-MB-231 cells, lactate transport, MCT1, alpha-ketoglutarate, interleukin-6, cell migration, 13C NMR
- MeSH terms
- Hypoxia, Breast Neoplasms, Carcinoma, Cell Communication, Female, Fibroblasts, Glycolysis, Humans, Stromal Cells, Lactic Acid, Paracrine Communication, Cell Line, Tumor, Metabolic Networks and Pathways, Tumor Microenvironment, Mesenchymal Stem Cells
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