Top

Published in:

01-06-2019 | Acidosis

Acidosis and proteolysis in the tumor microenvironment

Published in: Cancer and Metastasis Reviews | Issue 1-2/2019

Abstract

The glycolytic phenotype of the Warburg effect is associated with acidification of the tumor microenvironment. In this review, we describe how acidification of the tumor microenvironment may increase the invasive and degradative phenotype of cancer cells. As a template of an extracellular acidic microenvironment that is linked to proteolysis, we use the resorptive pit formed between osteoclasts and bone. We describe similar changes that have been observed in cancer cells in response to an acidic microenvironment and that are associated with proteolysis and invasive and metastatic phenotypes. This includes consideration of changes observed in the intracellular trafficking of vesicles, i.e., lysosomes and exosomes, and in specialized regions of the membrane, i.e., invadopodia and caveolae. Cancer-associated cells are known to affect what is generally referred to as tumor proteolysis but little direct evidence for this being regulated by acidosis; we describe potential links that should be verified.

Hanahan, D., & Weinberg, R. A. (2000). The hallmarks of cancer. Cell, 100(1), 57–70.CrossRef

Paget, S. (1989). The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Reviews, 8(2), 98–101.PubMed

Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: the next generation. Cell, 144(5), 646–674. https://doi.org/10.1016/j.cell.2011.02.013.CrossRefPubMed

Pietras, K., & Ostman, A. (2010). Hallmarks of cancer: interactions with the tumor stroma. Experimental Cell Research, 316(8), 1324–1331. https://doi.org/10.1016/j.yexcr.2010.02.045.CrossRefPubMed

Hanahan, D., & Coussens, L. M. (2012). Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell, 21(3), 309–322. https://doi.org/10.1016/j.ccr.2012.02.022.CrossRef

Pickup, M. W., Mouw, J. K., & Weaver, V. M. (2014). The extracellular matrix modulates the hallmarks of cancer. EMBO Reports, 15(12), 1243–1253. https://doi.org/10.15252/embr.201439246.CrossRefPubMedPubMedCentral

Kanada, M., Bachmann, M. H., & Contag, C. H. (2016). Signaling by extracellular vesicles advances cancer hallmarks. Trends Cancer, 2(2), 84–94. https://doi.org/10.1016/j.trecan.2015.12.005.CrossRefPubMed

Meehan, K., & Vella, L. J. (2016). The contribution of tumour-derived exosomes to the hallmarks of cancer. Critical Reviews in Clinical Laboratory Sciences, 53(2), 121–131. https://doi.org/10.3109/10408363.2015.1092496.CrossRefPubMed

Pavlova, N. N., & Thompson, C. B. (2016). The emerging hallmarks of cancer metabolism. Cell Metabolism, 23(1), 27–47. https://doi.org/10.1016/j.cmet.2015.12.006.CrossRefPubMedPubMedCentral

10.

Harguindey, S., Orive, G., Luis Pedraz, J., Paradiso, A., & Reshkin, S. J. (2005). The role of pH dynamics and the Na+/H+ antiporter in the etiopathogenesis and treatment of cancer. Two faces of the same coin--one single nature. Biochimica et Biophysica Acta, 1756(1), 1–24. https://doi.org/10.1016/j.bbcan.2005.06.004.CrossRefPubMed

11.

Ruan, K., Song, G., & Ouyang, G. (2009). Role of hypoxia in the hallmarks of human cancer. Journal of Cellular Biochemistry, 107(6), 1053–1062. https://doi.org/10.1002/jcb.22214.CrossRefPubMed

12.

Colotta, F., Allavena, P., Sica, A., Garlanda, C., & Mantovani, A. (2009). Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis, 30(7), 1073–1081. https://doi.org/10.1093/carcin/bgp127.CrossRefPubMed

13.

Warburg, O. (1925). The metabolism of carcinoma cells. Cancer Research, 9(1), 148–163. https://doi.org/10.1158/jcr.1925.148.CrossRef

14.

White, K. A., Grillo-Hill, B. K., & Barber, D. L. (2017). Cancer cell behaviors mediated by dysregulated pH dynamics at a glance. Journal of Cell Science, 130(4), 663–669. https://doi.org/10.1242/jcs.195297.CrossRefPubMedPubMedCentral

15.

Peppicelli, S., Andreucci, E., Ruzzolini, J., Margheri, F., Laurenzana, A., Bianchini, F., & Calorini, L. (2017). Acidity of microenvironment as a further driver of tumor metabolic reprogramming. Journal of Clinical & Cellular Immunology, 8, 485. https://doi.org/10.4172/2155-9899.1000485.CrossRef

16.

Gatenby, R. A., Gawlinski, E. T., Gmitro, A. F., Kaylor, B., & Gillies, R. J. (2006). Acid-mediated tumor invasion: a multidisciplinary study. Cancer Research, 66(10), 5216–5223. https://doi.org/10.1158/0008-5472.CAN-05-4193.CrossRefPubMed

17.

Gillies, R. J., & Gatenby, R. A. (2015). Metabolism and its sequelae in cancer evolution and therapy. Cancer Journal, 21(2), 88–96. https://doi.org/10.1097/PPO.0000000000000102.CrossRef

18.

Webb, B. A., Chimenti, M., Jacobson, M. P., & Barber, D. L. (2011). Dysregulated pH: a perfect storm for cancer progression. Nature Reviews. Cancer, 11(9), 671–677. https://doi.org/10.1038/nrc3110.CrossRefPubMed

19.

Teitelbaum, S. L. (2000). Bone resorption by osteoclasts. Science, 289(5484), 1504–1508.CrossRef

20.

Georgess, D., Machuca-Gayet, I., Blangy, A., & Jurdic, P. (2014). Podosome organization drives osteoclast-mediated bone resorption. Cell Adhesion & Migration, 8(3), 191–204.CrossRef

21.

Murphy, D. A., & Courtneidge, S. A. (2011). The ‘ins’ and ‘outs’ of podosomes and invadopodia: characteristics, formation and function. Nature Reviews. Molecular Cell Biology, 12(7), 413–426. https://doi.org/10.1038/nrm3141.CrossRefPubMedPubMedCentral

22.

Toyomura, T., Murata, Y., Yamamoto, A., Oka, T., Sun-Wada, G. H., Wada, Y., & Futai, M. (2003). From lysosomes to the plasma membrane: localization of vacuolar-type H+ -ATPase with the a3 isoform during osteoclast differentiation. The Journal of Biological Chemistry, 278(24), 22023–22030. https://doi.org/10.1074/jbc.M302436200.CrossRefPubMed

23.

Edwards, D., Hoyer-Hansen, G., Blasi, F., & Sloane, B. F. (2008). The cancer degradome: protease and cancer biology. New York: Springer.CrossRef

24.

DiCiccio, J. E., & Steinberg, B. E. (2011). Lysosomal pH and analysis of the counter ion pathways that support acidification. The Journal of General Physiology, 137(4), 385–390. https://doi.org/10.1085/jgp.201110596.CrossRefPubMedPubMedCentral

25.

Roshy, S., Sloane, B. F., & Moin, K. (2003). Pericellular cathepsin B and malignant progression. Cancer Metastasis Reviews, 22(2–3), 271–286.CrossRef

26.

Sloane, B. F., Yan, S., Podgorski, I., Linebaugh, B. E., Cher, M. L., Mai, J., et al. (2005). Cathepsin B and tumor proteolysis: contribution of the tumor microenvironment. Seminars in Cancer Biology, 15(2), 149–157. https://doi.org/10.1016/j.semcancer.2004.08.001.CrossRefPubMed

27.

Mohamed, M. M., & Sloane, B. F. (2006). Cysteine cathepsins: multifunctional enzymes in cancer. Nature Reviews. Cancer, 6(10), 764–775. https://doi.org/10.1038/nrc1949.CrossRefPubMed

28.

Corbet, C., & Feron, O. (2017). Tumour acidosis: from the passenger to the driver’s seat. Nature Reviews. Cancer, 17(10), 577–593. https://doi.org/10.1038/nrc.2017.77.CrossRefPubMed

29.

Podgorski, I., & Sloane, B. F. (2003). Cathepsin B and its role(s) in cancer progression. Biochemical Society Symposium, 70(70), 263–276.CrossRef

30.

Aggarwal, N., & Sloane, B. F. (2014). Cathepsin B: multiple roles in cancer. Proteomics. Clinical Applications, 8(5–6), 427–437. https://doi.org/10.1002/prca.201300105.CrossRefPubMedPubMedCentral

31.

Mason, S. D., & Joyce, J. A. (2011). Proteolytic networks in cancer. Trends in Cell Biology, 21(4), 228–237. https://doi.org/10.1016/j.tcb.2010.12.002.CrossRefPubMed

32.

Heuser, J. (1989). Changes in lysosome shape and distribution correlated with changes in cytoplasmic pH. The Journal of Cell Biology, 108(3), 855–864.CrossRef

33.

Kobayashi, H., Moniwa, N., Sugimura, M., Shinohara, H., Ohi, H., & Terao, T. (1993). Effects of membrane-associated cathepsin B on the activation of receptor-bound prourokinase and subsequent invasion of reconstituted basement membranes. Biochimica et Biophysica Acta, 1178(1), 55–62.CrossRef

34.

Andrade, L. O., & Andrews, N. W. (2005). The Trypanosoma cruzi-host-cell interplay: location, invasion, retention. Nature Reviews. Microbiology, 3(10), 819–823. https://doi.org/10.1038/nrmicro1249.CrossRefPubMed

35.

Chapman, H. A., Jr., Munger, J. S., & Shi, G. P. (1994). The role of thiol proteases in tissue injury and remodeling. American Journal of Respiratory and Critical Care Medicine, 150(6 Pt 2), S155–S159. https://doi.org/10.1164/ajrccm/150.6_Pt_2.S155.CrossRefPubMed

36.

Castro-Gomes, T., Corrotte, M., Tam, C., & Andrews, N. W. (2016). Plasma membrane repair is regulated extracellularly by proteases released from lysosomes. PLoS One, 11(3), e0152583. https://doi.org/10.1371/journal.pone.0152583.CrossRefPubMedPubMedCentral

37.

Sameni, M., Elliott, E., Ziegler, G., Fortgens, P. H., Dennison, C., & Sloane, B. F. (1995). Cathepsin B and D are localized at the surface of human breast cancer cells. Pathology Oncology Research, 1(1), 43–53.CrossRef

38.

Glunde, K., Guggino, S. E., Solaiyappan, M., Pathak, A. P., Ichikawa, Y., & Bhujwalla, Z. M. (2003). Extracellular acidification alters lysosomal trafficking in human breast cancer cells. Neoplasia, 5(6), 533–545.CrossRef

39.

Damaghi, M., Tafreshi, N. K., Lloyd, M. C., Sprung, R., Estrella, V., Wojtkowiak, J. W., Morse, D. L., Koomen, J. M., Bui, M. M., Gatenby, R. A., & Gillies, R. J. (2015). Chronic acidosis in the tumour microenvironment selects for overexpression of LAMP2 in the plasma membrane. Nature Communications, 6, 8752. https://doi.org/10.1038/ncomms9752.CrossRefPubMedPubMedCentral

40.

Dovmark, T. H., Saccomano, M., Hulikova, A., Alves, F., & Swietach, P. (2017). Connexin-43 channels are a pathway for discharging lactate from glycolytic pancreatic ductal adenocarcinoma cells. Oncogene, 36, 4538–4550. https://doi.org/10.1038/onc.2017.71.CrossRefPubMedPubMedCentral

41.

Bohn, T., Rapp, S., Luther, N., Klein, M., Bruehl, T. J., Kojima, N., Aranda Lopez, P., Hahlbrock, J., Muth, S., Endo, S., Pektor, S., Brand, A., Renner, K., Popp, V., Gerlach, K., Vogel, D., Lueckel, C., Arnold-Schild, D., Pouyssegur, J., Kreutz, M., Huber, M., Koenig, J., Weigmann, B., Probst, H. C., von Stebut, E., Becker, C., Schild, H., Schmitt, E., & Bopp, T. (2018). Tumor immunoevasion via acidosis-dependent induction of regulatory tumor-associated macrophages. Nature Immunology, 19(12), 1319–1329. https://doi.org/10.1038/s41590-018-0226-8.CrossRefPubMed

42.

Rohani, N., Hao, L., Alexis, M. S., Joughin, B. A., Krismer, K., Moufarrej, M. N., Soltis, A. R., Lauffenburger, D. A., Yaffe, M. B., Burge, C. B., Bhatia, S. N., & Gertler, F. B. (2019). Acidification of tumor at stromal boundaries drives transcriptome alterations associated with aggressive phenotypes. Cancer Research, 79, 1952–1966. https://doi.org/10.1158/0008-5472.CAN-18-1604.CrossRefPubMed

43.

Dykes, S. S., Steffan, J. J., & Cardelli, J. A. (2017). Lysosome trafficking is necessary for EGF-driven invasion and is regulated by p38 MAPK and Na+/H+ exchangers. BMC Cancer, 17(1), 672. https://doi.org/10.1186/s12885-017-3660-3.CrossRefPubMedPubMedCentral

44.

Steffan, J. J., Williams, B. C., Welbourne, T., & Cardelli, J. A. (2010). HGF-induced invasion by prostate tumor cells requires anterograde lysosome trafficking and activity of Na+-H+ exchangers. Journal of Cell Science, 123(Pt 7, 1151–1159. https://doi.org/10.1242/jcs.063644.CrossRefPubMedPubMedCentral

45.

Vasiljeva, O., Papazoglou, A., Kruger, A., Brodoefel, H., Korovin, M., Deussing, J., et al. (2006). Tumor cell-derived and macrophage-derived cathepsin B promotes progression and lung metastasis of mammary cancer. Cancer Research, 66(10), 5242–5250. https://doi.org/10.1158/0008-5472.CAN-05-4463.CrossRefPubMed

46.

Sevenich, L., Schurigt, U., Sachse, K., Gajda, M., Werner, F., Muller, S., Vasiljeva, O., Schwinde, A., Klemm, N., Deussing, J., Peters, C., & Reinheckel, T. (2010). Synergistic antitumor effects of combined cathepsin B and cathepsin Z deficiencies on breast cancer progression and metastasis in mice. Proceedings of the National Academy of Sciences of the United States of America, 107(6), 2497–2502. https://doi.org/10.1073/pnas.0907240107.CrossRefPubMedPubMedCentral

47.

Gould, C. M., & Courtneidge, S. A. (2014). Regulation of invadopodia by the tumor microenvironment. Cell Adhesion & Migration, 8(3), 226–235.CrossRef

48.

McNiven, M. A. (2013). Breaking away: matrix remodeling from the leading edge. Trends in Cell Biology, 23(1), 16–21. https://doi.org/10.1016/j.tcb.2012.08.009.CrossRefPubMed

49.

Di Martino, J., Henriet, E., Ezzoukhry, Z., Goetz, J. G., Moreau, V., & Saltel, F. (2016). The microenvironment controls invadosome plasticity. Journal of Cell Science, 129(9), 1759–1768. https://doi.org/10.1242/jcs.182329.CrossRefPubMed

50.

Paterson, E. K., & Courtneidge, S. A. (2018). Invadosomes are coming: new insights into function and disease relevance. The FEBS Journal, 285(1), 8–27. https://doi.org/10.1111/febs.14123.CrossRefPubMed

51.

Tu, C., Ortega-Cava, C. F., Chen, G., Fernandes, N. D., Cavallo-Medved, D., Sloane, B. F., Band, V., & Band, H. (2008). Lysosomal cathepsin B participates in the podosome-mediated extracellular matrix degradation and invasion via secreted lysosomes in v-Src fibroblasts. Cancer Research, 68(22), 9147–9156. https://doi.org/10.1158/0008-5472.CAN-07-5127.CrossRefPubMedPubMedCentral

52.

Kryczka, J., Papiewska-Pajak, I., Kowalska, M. A., & Boncela, J. (2019). Cathepsin B is upregulated and mediates ECM degradation in colon adenocarcinoma HT29 cells overexpressing snail. Cells, 8(3). https://doi.org/10.3390/cells8030203.

53.

Stachowiak, K., Tokmina, M., Karpinska, A., Sosnowska, R., & Wiczk, W. (2004). Fluorogenic peptide substrates for carboxydipeptidase activity of cathepsin B. Acta Biochimica Polonica, 51(1), 81–92.PubMed

54.

Busco, G., Cardone, R. A., Greco, M. R., Bellizzi, A., Colella, M., Antelmi, E., Mancini, M. T., Dell'Aquila, M. E., Casavola, V., Paradiso, A., & Reshkin, S. J. (2010). NHE1 promotes invadopodial ECM proteolysis through acidification of the peri-invadopodial space. The FASEB Journal, 24(10), 3903–3915. https://doi.org/10.1096/fj.09-149518.CrossRefPubMed

55.

Rothberg, J. M., Bailey, K. M., Wojtkowiak, J. W., Ben-Nun, Y., Bogyo, M., Weber, E., Moin, K., Blum, G., Mattingly, R. R., Gillies, R. J., & Sloane, B. F. (2013). Acid-mediated tumor proteolysis: contribution of cysteine cathepsins. Neoplasia, 15(10), 1125–1137.CrossRef

56.

Greco, M. R., Antelmi, E., Busco, G., Guerra, L., Rubino, R., Casavola, V., et al. (2014). Protease activity at invadopodial focal digestive areas is dependent on NHE1-driven acidic pHe. Oncology Reports, 31(2), 940–946. https://doi.org/10.3892/or.2013.2923.CrossRefPubMed

57.

Gasic, G. J., Boettiger, D., Catalfamo, J. L., Gasic, T. B., & Stewart, G. J. (1978). Aggregation of platelets and cell membrane vesiculation by rat cells transformed in vitro by Rous sarcoma virus. Cancer Research, 38(9), 2950–2955.PubMed

58.

Dvorak, H. F., Quay, S. C., Orenstein, N. S., Dvorak, A. M., Hahn, P., Bitzer, A. M., et al. (1981). Tumor shedding and coagulation. Science, 212(4497), 923–924.CrossRef

59.

Dvorak, H. F., Van DeWater, L., Bitzer, A. M., Dvorak, A. M., Anderson, D., Harvey, V. S., et al. (1983). Procoagulant activity associated with plasma membrane vesicles shed by cultured tumor cells. Cancer Research, 43(9), 4434–4442.PubMed

60.

Honn, K. V., Cavanaugh, P., Evens, C., Taylor, J. D., & Sloane, B. F. (1982). Tumor cell-platelet aggregation: induced by cathepsin B-like proteinase and inhibited by prostacyclin. Science, 217(4559), 540–542.CrossRef

61.

Becker, A., Thakur, B. K., Weiss, J. M., Kim, H. S., Peinado, H., & Lyden, D. (2016). Extracellular vesicles in cancer: cell-to-cell mediators of metastasis. Cancer Cell, 30(6), 836–848. https://doi.org/10.1016/j.ccell.2016.10.009.CrossRefPubMedPubMedCentral

62.

Parolini, I., Federici, C., Raggi, C., Lugini, L., Palleschi, S., De Milito, A., et al. (2009). Microenvironmental pH is a key factor for exosome traffic in tumor cells. The Journal of Biological Chemistry, 284(49), 34211–34222. https://doi.org/10.1074/jbc.M109.041152.CrossRefPubMedPubMedCentral

63.

Ban, J. J., Lee, M., Im, W., & Kim, M. (2015). Low pH increases the yield of exosome isolation. Biochemical and Biophysical Research Communications, 461(1), 76–79. https://doi.org/10.1016/j.bbrc.2015.03.172.CrossRefPubMed

64.

Martinez-Outschoorn, U. E., Sotgia, F., & Lisanti, M. P. (2015). Caveolae and signalling in cancer. Nature Reviews. Cancer, 15(4), 225–237. https://doi.org/10.1038/nrc3915.CrossRefPubMed

65.

Felicetti, F., Parolini, I., Bottero, L., Fecchi, K., Errico, M. C., Raggi, C., Biffoni, M., Spadaro, F., Lisanti, M. P., Sargiacomo, M., & Carè, A. (2009). Caveolin-1 tumor-promoting role in human melanoma. International Journal of Cancer, 125(7), 1514–1522. https://doi.org/10.1002/ijc.24451.CrossRefPubMedPubMedCentral

66.

Schillaci, O., Fontana, S., Monteleone, F., Taverna, S., Di Bella, M. A., Di Vizio, D., et al. (2017). Exosomes from metastatic cancer cells transfer amoeboid phenotype to non-metastatic cells and increase endothelial permeability: their emerging role in tumor heterogeneity. Scientific Reports, 7(1), 4711. https://doi.org/10.1038/s41598-017-05002-y.CrossRefPubMedPubMedCentral

67.

Boussadia, Z., Lamberti, J., Mattei, F., Pizzi, E., Puglisi, R., Zanetti, C., Pasquini, L., Fratini, F., Fantozzi, L., Felicetti, F., Fecchi, K., Raggi, C., Sanchez, M., D’Atri, S., Carè, A., Sargiacomo, M., & Parolini, I. (2018). Acidic microenvironment plays a key role in human melanoma progression through a sustained exosome mediated transfer of clinically relevant metastatic molecules. Journal of Experimental & Clinical Cancer Research, 37(1), 245. https://doi.org/10.1186/s13046-018-0915-z.CrossRef

68.

Palade, G. E. (1953). Fine structure of blood capillaries. Journal of Applied Physics, 24, 1424.

69.

Nichols, B. (2018). The mystery of caveolae. The Scientist, 42–47.

70.

Cheng, J. P. X., & Nichols, B. J. (2016). Caveolae: one function or many? Trends in Cell Biology, 26(3), 177–189. https://doi.org/10.1016/j.tcb.2015.10.010.CrossRefPubMed

71.

Cavallo-Medved, D., Dosescu, J., Linebaugh, B. E., Sameni, M., Rudy, D., & Sloane, B. F. (2003). Mutant K-ras regulates cathepsin B localization on the surface of human colorectal carcinoma cells. Neoplasia, 5(6), 507–519.CrossRef

72.

Bydoun, M., & Waisman, D. M. (2014). On the contribution of S100A10 and annexin A2 to plasminogen activation and oncogenesis: an enduring ambiguity. Future Oncology, 10(15), 2469–2479. https://doi.org/10.2217/fon.14.163.CrossRefPubMed

73.

Madureira, P. A., Bharadwaj, A. G., Bydoun, M., Garant, K., O'Connell, P., Lee, P., & Waisman, D. M. (2016). Cell surface protease activation during RAS transformation: critical role of the plasminogen receptor, S100A10. Oncotarget, 7(30), 47720–47737. https://doi.org/10.18632/oncotarget.10279.CrossRefPubMedPubMedCentral

74.

Zakrzewicz, D., Didiasova, M., Zakrzewicz, A., Hocke, A. C., Uhle, F., Markart, P., Preissner, K. T., & Wygrecka, M. (2014). The interaction of enolase-1 with caveolae-associated proteins regulates its subcellular localization. The Biochemical Journal, 460(2), 295–307. https://doi.org/10.1042/BJ20130945.CrossRefPubMed

75.

Stahl, A., & Mueller, B. M. (1995). The urokinase-type plasminogen activator receptor, a GPI-linked protein, is localized in caveolae. The Journal of Cell Biology, 129(2), 335–344.CrossRef

76.

Schwab, W., Gavlik, J. M., Beichler, T., Funk, R. H., Albrecht, S., Magdolen, V., et al. (2001). Expression of the urokinase-type plasminogen activator receptor in human articular chondrocytes: association with caveolin and beta 1-integrin. Histochemistry and Cell Biology, 115(4), 317–323.PubMed

77.

Kwon, M., MacLeod, T. J., Zhang, Y., & Waisman, D. M. (2005). S100A10, annexin A2, and annexin a2 heterotetramer as candidate plasminogen receptors. Frontiers in Bioscience, 10, 300–325.CrossRef

78.

Mai, J., Finley, R. L., Jr., Waisman, D. M., & Sloane, B. F. (2000). Human procathepsin B interacts with the annexin II tetramer on the surface of tumor cells. The Journal of Biological Chemistry, 275(17), 12806–12812.CrossRef

79.

Guo, M., Mathieu, P. A., Linebaugh, B., Sloane, B. F., & Reiners, J. J., Jr. (2002). Phorbol ester activation of a proteolytic cascade capable of activating latent transforming growth factor-betaL a process initiated by the exocytosis of cathepsin B. The Journal of Biological Chemistry, 277(17), 14829–14837. https://doi.org/10.1074/jbc.M108180200.CrossRefPubMed

80.

Cavallo-Medved, D., Mai, J., Dosescu, J., Sameni, M., & Sloane, B. F. (2005). Caveolin-1 mediates the expression and localization of cathepsin B, pro-urokinase plasminogen activator and their cell-surface receptors in human colorectal carcinoma cells. Journal of Cell Science, 118(Pt 7), 1493–1503. https://doi.org/10.1242/jcs.02278.CrossRefPubMed

81.

Deryugina, E. I., & Quigley, J. P. (2012). Cell surface remodeling by plasmin: a new function for an old enzyme. Journal of Biomedicine & Biotechnology, 2012, 564259. https://doi.org/10.1155/2012/564259.CrossRef

82.

Capello, M., Ferri-Borgogno, S., Riganti, C., Chattaragada, M. S., Principe, M., Roux, C., Zhou, W., Petricoin, E. F., Cappello, P., & Novelli, F. (2016). Targeting the Warburg effect in cancer cells through ENO1 knockdown rescues oxidative phosphorylation and induces growth arrest. Oncotarget, 7(5), 5598–5612. https://doi.org/10.18632/oncotarget.6798.CrossRefPubMed

83.

Laurenzana, A., Chilla, A., Luciani, C., Peppicelli, S., Biagioni, A., Bianchini, F., et al. (2017). uPA/uPAR system activation drives a glycolytic phenotype in melanoma cells. International Journal of Cancer, 141(6), 1190–1200. https://doi.org/10.1002/ijc.30817.CrossRefPubMed

84.

Brisson, L., Gillet, L., Calaghan, S., Besson, P., Le Guennec, J. Y., Roger, S., et al. (2011). Na(V)1.5 enhances breast cancer cell invasiveness by increasing NHE1-dependent H(+) efflux in caveolae. Oncogene, 30(17), 2070–2076. https://doi.org/10.1038/onc.2010.574.CrossRefPubMed

85.

Parton, R. G., & del Pozo, M. A. (2013). Caveolae as plasma membrane sensors, protectors and organizers. Nature Reviews. Molecular Cell Biology, 14(2), 98–112. https://doi.org/10.1038/nrm3512.CrossRefPubMed

86.

Dulhunty, A. F., & Franzini-Armstrong, C. (1975). The relative contributions of the folds and caveolae to the surface membrane of frog skeletal muscle fibres at different sarcomere lengths. The Journal of Physiology, 250(3), 513–539.CrossRef

87.

Nwosu, Z. C., Ebert, M. P., Dooley, S., & Meyer, C. (2016). Caveolin-1 in the regulation of cell metabolism: a cancer perspective. Molecular Cancer, 15(1), 71. https://doi.org/10.1186/s12943-016-0558-7.CrossRefPubMedPubMedCentral

88.

Shin, H., Haga, J. H., Kosawada, T., Kimura, K., Li, Y. S., Chien, S., & Schmid-Schönbein, G. W. (2019). Fine control of endothelial VEGFR-2 activation: caveolae as fluid shear stress shelters for membrane receptors. Biomechanics and Modeling in Mechanobiology, 18(1), 5–16. https://doi.org/10.1007/s10237-018-1063-2.CrossRefPubMed

89.

Sloane, B. F., List, K., Fingleton, B., & Matrisian, L. (2013). Proteases: structure and function. New York: Springer.

90.

Estrella, V., Chen, T., Lloyd, M., Wojtkowiak, J., Cornnell, H. H., Ibrahim-Hashim, A., Bailey, K., Balagurunathan, Y., Rothberg, J. M., Sloane, B. F., Johnson, J., Gatenby, R. A., & Gillies, R. J. (2013). Acidity generated by the tumor microenvironment drives local invasion. Cancer Research, 73(5), 1524–1535. https://doi.org/10.1158/0008-5472.CAN-12-2796.CrossRefPubMedPubMedCentral

91.

Giusti, I., D'Ascenzo, S., Millimaggi, D., Taraboletti, G., Carta, G., Franceschini, N., et al. (2008). Cathepsin B mediates the pH-dependent proinvasive activity of tumor-shed microvesicles. Neoplasia, 10(5), 481–488.CrossRef

92.

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., Pestell, R. G., Martinez-Outschoorn, U. E., Sotgia, F., & Lisanti, M. P. (2009). The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma. Cell Cycle, 8(23), 3984–4001. https://doi.org/10.4161/cc.8.23.10238.CrossRefPubMed

93.

Radhakrishnan, R., Ha, J. H., Jayaraman, M., Liu, J., Moxley, K. M., Isidoro, C., Sood, A. K., Song, Y. S., & Dhanasekaran, D. N. (2019). Ovarian cancer cell-derived lysophosphatidic acid induces glycolytic shift and cancer-associated fibroblast-phenotype in normal and peritumoral fibroblasts. Cancer Letters, 442, 464–474. https://doi.org/10.1016/j.canlet.2018.11.023.CrossRefPubMed

94.

Mills, G. B., & Moolenaar, W. H. (2003). The emerging role of lysophosphatidic acid in cancer. Nature Reviews. Cancer, 3(8), 582–591. https://doi.org/10.1038/nrc1143.CrossRefPubMed

95.

Pustilnik, T. B., Estrella, V., Wiener, J. R., Mao, M., Eder, A., Watt, M. A., et al. (1999). Lysophosphatidic acid induces urokinase secretion by ovarian cancer cells. Clinical Cancer Research, 5(11), 3704–3710.PubMed

96.

Fishman, D. A., Liu, Y., Ellerbroek, S. M., & Stack, M. S. (2001). Lysophosphatidic acid promotes matrix metalloproteinase (MMP) activation and MMP-dependent invasion in ovarian cancer cells. Cancer Research, 61(7), 3194–3199.PubMed

97.

Jeong, K. J., Park, S. Y., Cho, K. H., Sohn, J. S., Lee, J., Kim, Y. K., Kang, J., Park, C. G., Han, J. W., & Lee, H. Y. (2012). The rho/ROCK pathway for lysophosphatidic acid-induced proteolytic enzyme expression and ovarian cancer cell invasion. Oncogene, 31(39), 4279–4289. https://doi.org/10.1038/onc.2011.595.CrossRefPubMed

Title: Acidosis and proteolysis in the tumor microenvironment
Publication date: 01-06-2019
Keyword: Acidosis
Published in: Cancer and Metastasis Reviews / Issue 1-2/2019
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-019-09796-3

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1-2/2019

Exosomes, metastases, and the miracle of cancer stem cell markers

Fugitives on the run: circulating tumor cells (CTCs) in metastatic diseases

Correction to: Tumor pH and metastasis: a malignant process beyond hypoxia

Acidosis promotes tumorigenesis by activating AKT/NF-κB signaling

Pro-metastatic functions of lipoproteins and extracellular vesicles in the acidic tumor microenvironment

Preface

Keynote webinar | Spotlight on antibody–drug conjugates in cancer