Tissue proteomics in pancreatic cancer study: Discovery, emerging technologies, and challenges

Proteomics

Volumn 13, Issue 3-4, 2013, Pages 710-721

  Pan, Sheng ^a   Brentnall, Teresa A ^a   Kelly, Kimberly ^b   Chen, Ru ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

^b University of Virginia   (United States)

Author keywords

Biomedicine; Mass spectrometry; Pancreatic cancer; Pancreatitis; Tissue

Indexed keywords

ALPHA ACTININ 4; CATHEPSIN D; CD24 ANTIGEN; COFILIN; FORMALDEHYDE; GALECTIN 1; GELSOLIN; GEMCITABINE; HEAT SHOCK PROTEIN 27; HERMES ANTIGEN; INTEGRIN; LAMININ 1; LUMICAN; MICRORNA; MOESIN; OXYTHIAMINE; PROTEIN 14 3 3; PROTEIN S 100; RADIXIN; RETINOBLASTOMA BINDING PROTEIN; RETINOBLASTOMA BINDING PROTEIN 9; SUPEROXIDE DISMUTASE; TISSUE PLASMINOGEN ACTIVATOR; UNCLASSIFIED DRUG; VERSICAN;

CANCER CELL; CANCER INVASION; CANCER SURVIVAL; CARCINOGENESIS; CELL INTERACTION; CELL SURVIVAL; CHEMICAL REACTION; CHRONIC PANCREATITIS; FLUORESCENCE ACTIVATED CELL SORTING; FUNCTIONAL PROTEOMICS; HUMAN; IMMUNOHISTOCHEMISTRY; LASER CAPTURE MICRODISSECTION; LYMPH NODE METASTASIS; MASS SPECTROMETRY; MATRIX ASSISTED LASER DESORPTION IONIZATION TIME OF FLIGHT MASS SPECTROMETRY; MOLECULAR MECHANICS; PANCREAS ADENOCARCINOMA; PANCREAS ADENOMA; PANCREAS CANCER; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN INTERACTION; PROTEIN PROCESSING; PROTEOMICS; REVIEW; SENSITIVITY AND SPECIFICITY; SIGNAL TRANSDUCTION; STELLATE CELL; STEM CELL; STROMA CELL; TANDEM MASS SPECTROMETRY; TUMOR MICROENVIRONMENT; TWO DIMENSIONAL ELECTROPHORESIS;

ANIMALS; CELL LINE, TUMOR; HUMANS; MASS SPECTROMETRY; NEOPLASTIC STEM CELLS; PANCREATIC NEOPLASMS; PROTEOME; PROTEOMICS; SIGNAL TRANSDUCTION; TISSUE FIXATION;

EID: 84873988737     PISSN: 16159853     EISSN: 16159861     Source Type: Journal    
DOI: 10.1002/pmic.201200319     Document Type: Review

References (108)

1. Siegel, R., Desantis, C., Virgo, K., Stein, K. et al., Cancer treatment and survivorship statistics, 2012. CA Cancer J. Clin. 2012, 62, 220-241.
2. Siegel, R., Naishadham, D., Jemal, A., Cancer statistics, 2012. CA Cancer J. Clin. 2012, 62, 10-29.
3. de Godoy, L. M., Olsen, J. V., Cox, J., Nielsen, M. L. et al., Comprehensive mass-spectrometry-based proteome quantification of haploid versus diploid yeast. Nature 2008, 455, 1251-1254.
4. Gygi, S. P., Rochon, Y., Franza, B. R., Aebersold, R., Correlation between protein and mRNA abundance in yeast. Mol. Cell Biol. 1999, 19, 1720-1730.
5. Ideker, T., Thorsson, V., Ranish, J. A., Christmas, R. et al., Integrated genomic and proteomic analyses of a systematically perturbed metabolic network. Science 2001, 292, 929-934.
6. Cecconi, D., Palmieri, M., Donadelli, M., Proteomics in pancreatic cancer research. Proteomics 2011, 11, 816-828.
7. Chen, R., Pan, S., Aebersold, R., Brentnall, T., Proteomics studies of pancreatic cancer. Proteomics Clin. Appl. 2007, 1, 1582-1591.
8. Chen, R., Pan, S., Brentnall, T. A., Aebersold, R., Proteomic profiling of pancreatic cancer for biomarker discovery. Mol. Cell Proteomics 2005, 4, 523-533.
9. Grantzdorffer, I., Carl-McGrath, S., Ebert, M. P., Rocken, C., Proteomics of pancreatic cancer. Pancreas 2008, 36, 329-336.
10. Sun, C., Rosendahl, A. H., Ansari, D., Andersson, R., Proteome-based biomarkers in pancreatic cancer. World J. Gastroenterol. 2011, 17, 4845-4852.
11. Tonack, S., Aspinall-O'Dea, M., Neoptolemos, J. P., Costello, E., Pancreatic cancer: proteomic approaches to a challenging disease. Pancreatology 2009, 9, 567-576.
12. Aebersold, R., Goodlett, D. R., Mass spectrometry in proteomics. Chem. Rev. 2001, 101, 269-295.
13. Aebersold, R., Mann, M., Mass spectrometry-based proteomics. Nature 2003, 422, 198-207.
14. McDonald, W. H., Yates, J. R., III, Shotgun proteomics: integrating technologies to answer biological questions. Curr. Opin. Mol. Ther. 2003, 5, 302-309.
15. Eng, J., McCormack, A. L., Yates, J. R., An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database. J. Am. Soc. Mass Spectrom. 1994, 5, 976-989.
16. Perkins, D. N., Pappin, D. J., Creasy, D. M., Cottrell, J. S., Probability-based protein identification by searching sequence databases using mass spectrometry data. Electrophoresis 1999, 20, 3551-3567.
17. Craig, R., Beavis, R. C., TANDEM: matching proteins with tandem mass spectra. Bioinformatics 2004, 20, 1466-1467.
18. Mueller, L. N., Brusniak, M. Y., Mani, D. R., Aebersold, R., An assessment of software solutions for the analysis of mass spectrometry based quantitative proteomics data. J. Proteome Res. 2008, 7, 51-61.
19. Pan, S., Aebersold, R., Quantitative proteomics by stable isotope labeling and mass spectrometry. Methods Mol. Biol. 2007, 367, 209-218.
20. Gygi, S. P., Rist, B., Gerber, S. A., Turecek, F. et al., Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nat. Biotechnol. 1999, 17, 994-999.
21. Schmidt, A., Kellermann, J., Lottspeich, F., A novel strategy for quantitative proteomics using isotope-coded protein labels. Proteomics 2005, 5, 4-15.
22. Ross, P. L., Huang, Y. N., Marchese, J. N., Williamson, B. et al., Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents. Mol. Cell Proteomics 2004, 3, 1154-1169.
23. Thompson, A., Schafer, J., Kuhn, K., Kienle, S. et al., Tandem mass tags: a novel quantification strategy for comparative analysis of complex protein mixtures by MS/MS. Anal. Chem. 2003, 75, 1895-1904.
24. America, A. H., Cordewener, J. H., Comparative LC-MS: a landscape of peaks and valleys. Proteomics 2008, 8, 731-749.
25. Choi, H., Fermin, D., Nesvizhskii, A. I., Significance analysis of spectral count data in label-free shotgun proteomics. Mol. Cell Proteomics 2008, 7, 2373-2385.
26. Old, W. M., Meyer-Arendt, K., Aveline-Wolf, L., Pierce, K. G. et al., Comparison of label-free methods for quantifying human proteins by shotgun proteomics. Mol. Cell Proteomics 2005, 4, 1487-1502.
27. Ryu, S., Gallis, B., Goo, Y. A., Shaffer, S. A. et al., Comparison of a label-free quantitative proteomic method based on peptide ion current area to the isotope coded affinity tag method. Cancer Inform. 2008, 6, 243-255.
28. Bellew, M., Coram, M., Fitzgibbon, M., Igra, M. et al., A suite of algorithms for the comprehensive analysis of complex protein mixtures using high-resolution LC-MS. Bioinformatics 2006, 22, 1902-1909.
29. May, D., Liu, Y., Law, W., Fitzgibbon, M. et al., Peptide sequence confidence in accurate mass and time analysis and its use in complex proteomics experiments. J. Proteome Res. 2008, 7, 5148-5156.
30. May, D., Pan, S., Crispin, D. A., Lai, K. et al., Investigating neoplastic progression of ulcerative colitis with label-free comparative proteomics. J. Proteome Res. 2011, 10, 200-209.
31. Wang, P., Tang, H., Zhang, H., Whiteaker, J. et al., Normalization regarding non-random missing values in high-throughput mass spectrometry data. Pac. Symp. Biocomput. 2006, 315-326.
32. Boja, E. S., Rodriguez, H., Mass spectrometry-based targeted quantitative proteomics: achieving sensitive and reproducible detection of proteins. Proteomics 2012, 12, 1093-1110.
33. Elschenbroich, S., Kislinger, T., Targeted proteomics by selected reaction monitoring mass spectrometry: applications to systems biology and biomarker discovery. Mol. Biosyst. 2011, 7, 292-303.
34. Gallien, S., Duriez, E., Domon, B., Selected reaction monitoring applied to proteomics. J. Mass Spectrom. 2011, 46, 298-312.
35. Huttenhain, R., Malmstrom, J., Picotti, P., Aebersold, R., Perspectives of targeted mass spectrometry for protein biomarker verification. Curr. Opin. Chem. Biol. 2009, 13, 518-525.
36. Meng, Z. and Veenstra, T. D., Targeted mass spectrometry approaches for protein biomarker verification. J. Proteomics 2011, 74, 2650-2659.
37. Pan, S., Aebersold, R., Chen, R., Rush, J. et al., Mass spectrometry based targeted protein quantification: methods and applications. J. Proteome Res. 2009, 8, 787-797.
38. Schiess, R., Wollscheid, B., Aebersold, R., Targeted proteomic strategy for clinical biomarker discovery. Mol. Oncol. 2009, 3, 33-44.
39. Gillet, L. C., Navarro, P., Tate, S., Rost, H. et al., Targeted data extraction of the MS/MS spectra generated by data-independent acquisition: a new concept for consistent and accurate proteome analysis. Mol. Cell Proteomics 2012, 11, O111.016717.
40. Neesse, A., Michl, P., Frese, K. K., Feig, C. et al., Stromal biology and therapy in pancreatic cancer. Gut 2011, 60, 861-868.
41. Liotta, L. A., Kohn, E. C., The microenvironment of the tumour-host interface. Nature 2001, 411, 375-379.
42. Wernert, N., The multiple roles of tumour stroma. Virchows Arch. 1997, 430, 433-443.
43. Brown, L. F., Guidi, A. J., Schnitt, S. J., Van De, W. L. et al., Vascular stroma formation in carcinoma in situ, invasive carcinoma, and metastatic carcinoma of the breast. Clin. Cancer Res. 1999, 5, 1041-1056.
44. Chen, R., Yi, E. C., Donohoe, S., Pan, S. et al., Pancreatic cancer proteome: the proteins that underlie invasion, metastasis, and immunologic escape. Gastroenterology 2005, 129, 1187-1197.
45. Lu, Z., Hu, L., Evers, S., Chen, J. et al., Differential expression profiling of human pancreatic adenocarcinoma and healthy pancreatic tissue. Proteomics 2004, 4, 3975-3988.
46. Shen, J., Person, M. D., Zhu, J., Abbruzzese, J. L. et al., Protein expression profiles in pancreatic adenocarcinoma compared with normal pancreatic tissue and tissue affected by pancreatitis as detected by two-dimensional gel electrophoresis and mass spectrometry. Cancer Res. 2004, 64, 9018-9026.
47. Pan, S., Chen, R., Brand, R. E., Hawley, S. et al., Multiplex targeted proteomic assay for biomarker detection in plasma: a pancreatic cancer biomarker case study. J. Proteome Res. 2012, 11, 1937-1948.
48. Bausch, D., Thomas, S., Mino-Kenudson, M., Fernandez, D. et al., Plectin-1 as a novel biomarker for pancreatic cancer. Clin. Cancer Res. 2011, 17, 302-309.
49. Kelly, K. A., Bardeesy, N., Anbazhagan, R., Gurumurthy, S. et al., Targeted nanoparticles for imaging incipient pancreatic ductal adenocarcinoma. PLoS Med. 2008, 5, e85.
50. Wang, Y., Kuramitsu, Y., Ueno, T., Suzuki, N. et al., Differential expression of up-regulated cofilin-1 and down-regulated cofilin-2 characteristic of pancreatic cancer tissues. Oncol. Rep. 2011, 26, 1595-1599.
51. Cui, Y., Wu, J., Zong, M., Song, G. et al., Proteomic profiling in pancreatic cancer with and without lymph node metastasis. Int. J. Cancer 2009, 124, 1614-1621.
52. Naidoo, K., Jones, R., Dmitrovic, B., Wijesuriya, N. et al., Proteome of formalin-fixed paraffin-embedded pancreatic ductal adenocarcinoma and lymph node metastases. J. Pathol. 2012, 226, 756-763.
53. Neupane, D., Korc, M., 14-3-3 sigma modulates pancreatic cancer cell survival and invasiveness. Clin. Cancer Res. 2008, 14, 7614-7623.
54. Roda, O., Ortiz-Zapater, E., Martinez-Bosch, N., Gutierrez-Gallego, R. et al., Galectin-1 is a novel functional receptor for tissue plasminogen activator in pancreatic cancer. Gastroenterology 2009, 136, 1379-1385.
55. Chen, R., Pan, S., Ottenhof, N., de Wilde, R. et al., Stromal galectin-1 expression is associated with long-term survival in resectable pancreatic ductal adenocarcinoma. Cancer Biol. Ther. 2012, 13, 899-907.
56. Pan, S., Chen, R., Reimel, B. A., Crispin, D. A. et al., Quantitative proteomics investigation of pancreatic intraepithelial neoplasia. Electrophoresis 2009, 30, 1132-1144.
57. Rhim, A. D., Mirek, E. T., Aiello, N. M., Maitra, A. et al., EMT and dissemination precede pancreatic tumor formation. Cell 2012, 148, 349-361.
58. Cui, Y., Tian, M., Zong, M., Teng, M. et al., Proteomic analysis of pancreatic ductal adenocarcinoma compared with normal adjacent pancreatic tissue and pancreatic benign cystadenoma. Pancreatology 2009, 9, 89-98.
59. Lowenfels, A. B., Maisonneuve, P., Cavallini, G., Ammann, R. W. et al., Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group. N. Engl. J. Med. 1993, 328, 1433-1437.
60. Malka, D., Hammel, P., Maire, F., Rufat, P. et al., Risk of pancreatic adenocarcinoma in chronic pancreatitis. Gut 2002, 51, 849-852.
61. Rosty, C., Geradts, J., Sato, N., Wilentz, R. E. et al., p16 inactivation in pancreatic intraepithelial neoplasias (PanINs) arising in patients with chronic pancreatitis. Am. J. Surg. Pathol. 2003, 27, 1495-1501.
62. Crnogorac-Jurcevic, T., Gangeswaran, R., Bhakta, V., Capurso, G. et al., Proteomic analysis of chronic pancreatitis and pancreatic adenocarcinoma. Gastroenterology 2005, 129, 1454-1463.
63. Chen, R., Brentnall, T. A., Pan, S., Cooke, K. et al., Quantitative proteomics analysis reveals that proteins differentially expressed in chronic pancreatitis are also frequently involved in pancreatic cancer. Mol. Cell Proteomics 2007, 6, 1331-1342.
64. Pan, S., Chen, R., Stevens, T., Bronner, M. P. et al., Proteomics portrait of archival lesions of chronic pancreatitis. PLoS One 2011, 6, e27574.
65. Dvorak, H. F., Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N. Engl. J. Med. 1986, 315, 1650-1659.
66. Blonder, J., Veenstra, T. D., Clinical proteomic applications of formalin-fixed paraffin-embedded tissues. Clin. Lab Med. 2009, 29, 101-113.
67. Hood, B. L., Conrads, T. P., Veenstra, T. D., Mass spectrometric analysis of formalin-fixed paraffin-embedded tissue: unlocking the proteome within. Proteomics 2006, 6, 4106-4114.
68. Ralton, L. D., Murray, G. I., The use of formalin fixed wax embedded tissue for proteomic analysis. J. Clin. Pathol. 2011, 64, 297-302.
69. Bell, L. N., Saxena, R., Mattar, S. G., You, J. et al., Utility of formalin-fixed, paraffin-embedded liver biopsy specimens for global proteomic analysis in nonalcoholic steatohepatitis. Proteomics Clin. Appl. 2011, 5, 397-404.
70. Hood, B. L., Darfler, M. M., Guiel, T. G., Furusato, B. et al., Proteomic analysis of formalin-fixed prostate cancer tissue. Mol. Cell Proteomics 2005, 4, 1741-1753.
71. Hwang, S. I., Thumar, J., Lundgren, D. H., Rezaul, K. et al., Direct cancer tissue proteomics: a method to identify candidate cancer biomarkers from formalin-fixed paraffin-embedded archival tissues. Oncogene 2007, 26, 65-76.
72. Negishi, A., Masuda, M., Ono, M., Honda, K. et al., Quantitative proteomics using formalin-fixed paraffin-embedded tissues of oral squamous cell carcinoma. Cancer Sci. 2009, 100, 1605-1611.
73. Tanca, A., Addis, M. F., Pagnozzi, D., Cossu-Rocca, P. et al., Proteomic analysis of formalin-fixed, paraffin-embedded lung neuroendocrine tumor samples from hospital archives. J. Proteomics 2011, 74, 359-370.
74. Cheung, W., Darfler, M. M., Alvarez, H., Hood, B. L. et al., Application of a global proteomic approach to archival precursor lesions: deleted in malignant brain tumors 1 and tissue transglutaminase 2 are upregulated in pancreatic cancer precursors. Pancreatology 2008, 8, 608-616.
75. Shields, D. J., Niessen, S., Murphy, E. A., Mielgo, A. et al., RBBP9: a tumor-associated serine hydrolase activity required for pancreatic neoplasia. Proc. Natl. Acad. Sci. U.S.A. 2010, 107, 2189-2194.
76. Funel, N., Giovannetti, E., Pollina, L. E., del Chiaro, M. et al., Critical role of laser microdissection for genetic, epigenetic and proteomic analyses in pancreatic cancer. Expert Rev. Mol. Diagn. 2011, 11, 695-701.
77. Gutstein, H. B., Morris, J. S., Laser capture sampling and analytical issues in proteomics. Expert Rev. Proteomics 2007, 4, 627-637.
78. Mustafa, D., Kros, J. M., Luider, T., Combining laser capture microdissection and proteomics techniques. Methods Mol. Biol. 2008, 428, 159-178.
79. Shekouh, A. R., Thompson, C. C., Prime, W., Campbell, F. et al., Application of laser capture microdissection combined with two-dimensional electrophoresis for the discovery of differentially regulated proteins in pancreatic ductal adenocarcinoma. Proteomics 2003, 3, 1988-2001.
80. Fu, A. Y., Spence, C., Scherer, A., Arnold, F. H., Quake, S. R., A microfabricated fluorescence-activated cell sorter. Nat. Biotechnol. 1999, 17, 1109-1111.
81. Kellner, U., Steinert, R., Seibert, V., Heim, S. et al., Epithelial cell preparation for proteomic and transcriptomic analysis in human pancreatic tissue. Pathol. Res. Pract. 2004, 200, 155-163.
82. Sheikh, A. A., Vimalachandran, D., Thompson, C. C., Jenkins, R. E. et al., The expression of S100A8 in pancreatic cancer-associated monocytes is associated with the Smad4 status of pancreatic cancer cells. Proteomics 2007, 7, 1929-1940.
83. Li, C., Heidt, D. G., Dalerba, P., Burant, C. F. et al., Identification of pancreatic cancer stem cells. Cancer Res. 2007, 67, 1030-1037.
84. Dai, L., Li, C., Shedden, K. A., Lee, C. J. et al., Quantitative proteomic profiling studies of pancreatic cancer stem cells. J. Proteome Res. 2010, 9, 3394-3402.
85. Balic, A., Dorado, J., Alonso-Gomez, M., Heeschen, C., Stem cells as the root of pancreatic ductal adenocarcinoma. Exp. Cell Res. 2012, 318, 691-704.
86. Seeley, E. H., Schwamborn, K., Caprioli, R. M., Imaging of intact tissue sections: moving beyond the microscope. J. Biol. Chem. 2011, 286, 25459-25466.
87. Minerva, L., Clerens, S., Baggerman, G., Arckens, L., Direct profiling and identification of peptide expression differences in the pancreas of control and ob/ob mice by imaging mass spectrometry. Proteomics 2008, 8, 3763-3774.
88. Green-Mitchell, S. M., Cazares, L. H., Semmes, O. J., Nadler, J. L. et al., On-tissue identification of insulin: in situ reduction coupled with mass spectrometry imaging. Proteomics Clin. Appl. 2011, 5, 448-453.
89. Djidja, M. C., Claude, E., Snel, M. F., Scriven, P. et al., MALDI-ion mobility separation-mass spectrometry imaging of glucose-regulated protein 78 kDa (Grp78) in human formalin-fixed, paraffin-embedded pancreatic adenocarcinoma tissue sections. J. Proteome Res. 2009, 8, 4876-4884.
90. Erkan, M., Adler, G., Apte, M. V., Bachem, M. G. et al., StellaTUM: current consensus and discussion on pancreatic stellate cell research. Gut 2012, 61, 172-178.
91. Paulo, J. A., Urrutia, R., Banks, P. A., Conwell, D. L. et al., Proteomic analysis of an immortalized mouse pancreatic stellate cell line identifies differentially-expressed proteins in activated vs nonproliferating cell states. J. Proteome Res. 2011, 10, 4835-4844.
92. Andreasen, P. A., Egelund, R., Petersen, H. H., The plasminogen activation system in tumor growth, invasion, and metastasis. Cell Mol. Life Sci. 2000, 57, 25-40.
93. Roda, O., Chiva, C., Espuna, G., Gabius, H. J. et al., A proteomic approach to the identification of new tPA receptors in pancreatic cancer cells. Proteomics 2006, 6(Suppl 1), S36-S41.
94. Hajjar, K. A., Krishnan, S., Annexin II: a mediator of the plasmin/plasminogen activator system. Trends Cardiovasc. Med. 1999, 9, 128-138.
95. Kuramitsu, Y., Taba, K., Ryozawa, S., Yoshida, K. et al., Identification of up- and down-regulated proteins in gemcitabine-resistant pancreatic cancer cells using two-dimensional gel electrophoresis and mass spectrometry. Anticancer Res. 2010, 30, 3367-3372.
96. Kuramitsu, Y., Wang, Y., Taba, K., Suenaga, S. et al., Heat-shock protein 27 plays the key role in gemcitabine-resistance of pancreatic cancer cells. Anticancer Res. 2012, 32, 2295-2299.
97. Mori-Iwamoto, S., Kuramitsu, Y., Ryozawa, S., Mikuria, K. et al., Proteomics finding heat shock protein 27 as a biomarker for resistance of pancreatic cancer cells to gemcitabine. Int. J. Oncol. 2007, 31, 1345-1350.
98. Mori-Iwamoto, S., Kuramitsu, Y., Ryozawa, S., Taba, K. et al., A proteomic profiling of gemcitabine resistance in pancreatic cancer cell lines. Mol. Med. Rep. 2008, 1, 429-434.
99. Chen, Y. W., Liu, J. Y., Lin, S. T., Li, J. M. et al., Proteomic analysis of gemcitabine-induced drug resistance in pancreatic cancer cells. Mol. Biosyst. 2011, 7, 3065-3074.
100. Zhou, J., Du, Y., Acquisition of resistance of pancreatic cancer cells to 2-methoxyestradiol is associated with the upregulation of manganese superoxide dismutase. Mol. Cancer Res. 2012, 10, 768-777.
101. Poland, J., Urbani, A., Lage, H., Schnolzer, M. et al., Study of the development of thermoresistance in human pancreatic carcinoma cell lines using proteome analysis. Electrophoresis 2004, 25, 173-183.
102. Yang, Y., Chaerkady, R., Kandasamy, K., Huang, T. C. et al., Identifying targets of miR-143 using a SILAC-based proteomic approach. Mol. Biosyst. 2010, 6, 1873-1882.
103. Stylli, S. S., Kaye, A. H., Lock, P., Invadopodia: at the cutting edge of tumour invasion. J. Clin. Neurosci. 2008, 15, 725-737.
104. Brentnall, T. A., Lai, L. A., Coleman, J., Bronner, M. P. et al., Arousal of cancer-associated stroma: overexpression of palladin activates fibroblasts to promote tumor invasion. PLoS One 2012, 7, e30219.
105. Salaria, S. N., Illei, P., Sharma, R., Walter, K. M. et al., Palladin is overexpressed in the non-neoplastic stroma of infiltrating ductal adenocarcinomas of the pancreas, but is only rarely overexpressed in neoplastic cells. Cancer Biol. Ther. 2007, 6, 324-328.
106. Harsha, H. C., Jimeno, A., Molina, H., Mihalas, A. B. et al., Activated epidermal growth factor receptor as a novel target in pancreatic cancer therapy. J. Proteome Res. 2008, 7, 4651-4658.
107. Zhang, H., Cao, R., Lee, W. N., Deng, C. et al., Inhibition of protein phosphorylation in MIA pancreatic cancer cells: confluence of metabolic and signaling pathways. J. Proteome Res. 2010, 9, 980-989.
108. Taba, K., Kuramitsu, Y., Ryozawa, S., Yoshida, K. et al., Heat-shock protein 27 is phosphorylated in gemcitabine-resistant pancreatic cancer cells. Anticancer Res. 2010, 30, 2539-2543.