Uptake of Cystatin by Melanoma Cells in Culture

Abstract

The cystatins are a super family of cysteine protease inhibitors which are ubiquitous in their biologic occurrence. Cystatin C, a type II cystatin, is primarily a secreted protein found in most biological fluids. Besides acting as inhibitors of cathepsin, the cystatins have been found to have some non-inhibitor related functions and multiple physiological roles. Much interest has been generated for the cystatins as metastasissuppressor-like proteins, as they have been shown to inhibit metastasis for multiple cancer types. The sites and actions of the cystatins related to tumor suppressor actions are still unclear, however. In this work, we have examined the uptake of cystatin by metastatic melanoma cells in culture. Our results indicate cystatin uptake is mediated by a non-canonical endocytotic pathway in B16 murine melanoma cells.

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L. Deady and J. Cox, "Uptake of Cystatin by Melanoma Cells in Culture," CellBio, Vol. 2 No. 2, 2013, pp. 64-69. doi: 10.4236/cellbio.2013.22008.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] V. Turk, V. Stoka and D. Turk, “Cystatins: Biochemical and Structural Properties, and Medical Relevance,” Frontiers in Bioscience: A Journal and Virtual Library, Vol. 13, 2008, pp. 5406-5420.
[2] M. F. Blankenvoorde, W. van’t Hof, E. Walgreen-Weterings, T. J. van Steenbergen, H. S. Brand, E. C. Veerman and A. V. N. Amerongen, “Cystatin and Cystatin-Derived Peptides Have Antibacterial Activity against the Pathogen Porphyromonas gingivalis,” Biological Chemistry, Vol. 379, No. 11, 1998, pp. 1371-1375.
[3] N. Kopitar-Jerala, “The Role of Cystatins in Cells of the Immune System,” FEBS Letters, Vol. 580, No. 27, 2006, pp. 6295-6301. doi:10.1016/j.febslet.2006.10.055
[4] Q. Sun, “Growth Stimulation of 3T3 Fibroblasts by Cystatin,” Experimental Cell Research, Vol. 180, No. 1, 1989, pp. 150-160. doi:10.1016/0014-4827(89)90219-X
[5] M. Abrahamson, A. J. Barrett, G. Salvesen and A. Grubb, “Isolation of Six Cysteine Proteinase Inhibitors from Human Urine. Their Physicochemical and Enzyme Kinetic Properties and Concentrations in Biological Fluids,” The Journal of Biological Chemistry, Vol. 261, No. 24, 1986, pp. 11282-11289.
[6] H. Wallin, M. Bjarnadottir, L. K. Vogel, J. Wassélius, U. Ekström and M. Abrahamson, “Cystatins—Extra- and Intracellular Cysteine Protease Inhibitors: High-Level Secretion and Uptake of Cystatin C in Human Neuroblastoma Cells.,” Biochimie, Vol. 92, No. 11, 2010, pp. 1625-1634. doi:10.1016/j.biochi.2010.08.011
[7] J. Wassélius, K. Johansson, K. Hakansson, M. Abrahamson and B. Ehinger, “Cystatin C Uptake in the Eye,” Graefe’s Archive for Clinical and Experimental Ophthalmology = Albrecht von Graefes Archiv für klinische und experimentelle Ophthalmologie, Vol. 243, No. 6, 2005, pp. 583-592.
[8] H. Ervin and J. L. Cox, “Late Stage Inhibition of Hematogenous Melanoma Metastasis by Cystatin C Over-Expression,” Cancer Cell International, Vol. 5, No. 1, 2005, p. 14. doi:10.1186/1475-2867-5-14
[9] W. Li, F. Ding, L. Zhang, Z. Liu, Y. Wu, A. Luo, M. Wu, M. Wang, Q. Zhan and Z. Liu, “Overexpression of Stefin A in Human Esophageal Squamous Cell Carcinoma Cells Inhibits Tumor Cell Growth, Angiogenesis, Invasion, and Metastasis,” Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, Vol. 11, No. 24, 2005, pp. 8753-8762.
[10] S. D. Konduri, N. Yanamandra, K. Siddique, A. Joseph, D. H. Dinh, W. C. Olivero, M. Gujrati, G. Kouraklis, A. Swaroop, A. P. Kyritsis and J. S. Rao, “Modulation of Cystatin C Expression Impairs the Invasive and Tumorigenic Potential of Human Glioblastoma Cells,” Oncogene, Vol. 21, No. 57, 2002, pp. 8705-8712. doi:10.1038/sj.onc.1205949
[11] B. Wegiel, T. Jiborn, M. Abrahamson, L. Helczynski, L. Otterbein, J. L. Persson and A. Bjartell, “Cystatin C Is Downregulated in Prostate Cancer and Modulates Invasion of Prostate Cancer Cells via MAPK/Erk and Androgen Receptor Pathways,” PloS One, Vol. 4, No. 11, 2009, e7953. doi:10.1371/journal.pone.0007953
[12] S. Alvarez-Díaz, N. Valle, J. M. García, C. Peña, J. M. P. Freije, V. Quesada, A. Astudillo, F. Bonilla, C. López-Otín and A. Muñoz, “Cystatin D Is a Candidate Tumor Suppressor Gene Induced by Vitamin D in Human Colon Cancer Cells.,” The Journal of Clinical Investigation, Vol. 119, No. 8, 2009, pp. 2343-2358. doi:10.1172/JCI37205
[13] J. P. Sokol and W. P. Schiemann, “Cystatin C Antagonizes Transforming Growth Factor Beta Signaling in Normal and Cancer Cells,” Molecular Cancer Research: MCR, Vol. 2, No. 3, 2004, pp. 183-195.
[14] J. Song, C. Jie, P. Polk, R. Shridhar, T. Clair, J. Zhang, L. Yin and D. Keppler, “The Candidate Tumor Suppressor CST6 Alters the Gene Expression Profile of Human Breast Carcinoma Cells: Down-Regulation of the Potent Mitogenic, Motogenic, and Angiogenic Factor Autotaxin,” Biochemical and Biophysical Research Communications, Vol. 340, No. 1, 2006, pp. 175-182. doi:10.1016/j.bbrc.2005.11.171
[15] D. Cavallo-Medved and B. F. Sloane, “Cell-Surface Cathepsin B: Understanding Its Functional Significance,” Current Topics in Developmental Biology, Vol. 54, 2003, pp. 313-341. doi:10.1016/S0070-2153(03)54013-3
[16] K. T. Chan, C. L. Cortesio and A. Huttenlocher, “Integrins in Cell Migration,” Methods in Enzymology, Vol. 426, 2007, pp. 47-67. doi:10.1016/S0076-6879(07)26003-3
[17] J. Ochieng and G. Chaudhuri, “Cystatin Superfamily,” Journal of Health Care for the Poor and Underserved, Vol. 21, No. 1, 2010, pp. 51-70. doi:10.1353/hpu.0.0257
[18] J. L. Cox, “Cystatins and Cancer,” Frontiers in Bioscience: A Journal and Virtual Library, Vol. 14, 2009, pp. 463-474.
[19] G. Bathori, L. Cervenak and I. Karadi, “Caveolae—An Alternative Endocytotic Pathway for Targeted Drug Delivery,” Critical Reviews in Therapeutic Drug Carrier Systems, Vol. 21, No. 2, 2004, pp. 67-95. doi:10.1615/CritRevTherDrugCarrierSyst.v21.i2.10
[20] K. M. Hussain, K. L. J. Leong, M. M.-L. Ng and J. J. H. Chu, “The Essential Role of Clathrin-Mediated Endocytosis in the Infectious Entry of Human Enterovirus 71,” The Journal of Biological Chemistry, Vol. 286, No. 1, 2011, pp. 309-321. doi:10.1074/jbc.M110.168468
[21] M. Rey, A. Valenzuela-Fernández, A. Urzainqui, M. Yáñez-Mó, M. Pérez-Martínez, P. Penela, F. Mayor and F. Sánchez-Madrid, “Myosin IIA Is Involved in the Endocytosis of CXCR4 Induced by SDF-1alpha.,” Journal of Cell Science, Vol. 120, No. 6, 2007, pp. 1126-1133.
[22] M. Bohdanowicz, G. Cosío, J. M. Backer and S. Grinstein, “Class I and Class III Phosphoinositide 3-Kinases Are Required for Actin Polymerization That Propels Phagosomes,” The Journal of Cell Biology, Vol. 191, No. 5, 2010, pp. 999-1012. doi:10.1083/jcb.201004005
[23] L. Lugini, P. Matarrese, A. Tinari, F. Lozupone, C. Federici, E. Iessi, M. Gentile, F. Luciani, G. Parmiani, L. Rivoltini, W. Malorni and S. Fais, “Cannibalism of Live Lymphocytes by Human Metastatic but Not Primary Melanoma Cells.,” Cancer Research, Vol. 66, No. 7, 2006, pp. 3629-3638. doi:10.1158/0008-5472.CAN-05-3204
[24] C. Federici, D. Brambilla, F. Lozupone, P. Matarrese, A. de Milito, L. Lugini, E. Iessi, S. Cecchetti, M. Marino, M. Perdicchio, M. Logozzi, M. Spada, W. Malorni and S. Fais, “Pleiotropic Function of Ezrin in Human Metastatic Melanomas,” International Journal of Cancer, Vol. 124, No. 12, 2009, pp. 2804-2812.
[25] U. Ekström, H. Wallin, J. Lorenzo, B. Holmqvist, M. Abrahamson and F. X. Avilés, “Internalization of Cystatin C in Human Cell Lines,” The FEBS Journal, Vol. 275, No. 18, 2008, pp. 4571-4582. doi:10.1111/j.1742-4658.2008.06600.x

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