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Acidosis and proteolysis in the tumor microenvironment

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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.

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References

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

    Article  CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  3. 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.

    Article  CAS  PubMed  Google Scholar 

  4. 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.

    Article  CAS  PubMed  Google Scholar 

  5. 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.

    Article  CAS  Google Scholar 

  6. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. 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.

    Article  PubMed  Google Scholar 

  8. 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.

    Article  CAS  PubMed  Google Scholar 

  9. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

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

    Book  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  Google Scholar 

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

    Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

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

    Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, 48201, USA

    Kyungmin Ji, Linda Mayernik, Kamiar Moin & Bonnie F. Sloane

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Ji, K., Mayernik, L., Moin, K. et al. Acidosis and proteolysis in the tumor microenvironment. Cancer Metastasis Rev 38, 103–112 (2019). https://doi.org/10.1007/s10555-019-09796-3

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