Advertisement

Heat Shock Protein Expression and Implications in Spontaneous Animal Tumors: Veterinary and Comparative Aspects

  • Mariarita Romanucci
  • Leonardo Della Salda
Chapter
Part of the Heat Shock Proteins book series (HESP, volume 12)

Abstract

Heat shock proteins (HSP) play a fundamental role in the maintenance of cellular homeostasis, under both physiological and stress conditions, by acting as molecular chaperones in protein folding, intracellular transport and degradation. HSP are also implicated in the hallmarks of cancer from proliferation, impaired apoptosis and sustained angiogenesis to invasion and metastasis. Altered HSP levels have been observed in a variety of human neoplasms and such abnormal expression may contribute to poor prognosis and drug resistance. Therefore, these molecular chaperones represent attractive targets for anti-cancer therapy. A growing number of studies in veterinary medicine have also demonstrated the presence of altered HSP expression in spontaneous animal tumors, especially canine cancer, and the study of carcinogenesis and the role of HSP in animal models represent an additional source of information for clinical cancer research. This chapter briefly reviews the current knowledge on HSP expression and implications in spontaneous animal neoplasms, and the advances in understanding of the therapeutic opportunities offered by HSP-based anti-cancer therapies in veterinary and comparative oncology.

Keywords

Animal model Cancer Comparative oncology Dog Spontaneous tumors 

Abbreviations

3-MA

3-methyladenine

APCs

Antigen-presenting cells

AR

Androgen receptor

BPH

Benign prostatic hyperplasia

CMTs

Canine mammary tumors

CTVT

Canine transmissible venereal tumor

GA

Geldanamycin

GISTs

Gastrointestinal stromal tumors

gp96

glycoprotein 96

Grp78

Glucose-regulated protein 78

HO-1

Heme oxygenase-1

HSP

Heat shock proteins

HSPPC

HSP–peptide complexes

HUGO

Human Genome Organization

MCs

Mast cells

MCTs

Mast cell tumors

MHC

Major histocompatibility complex

OS

Overall survival

OSA

Osteosarcoma

PCa

Prostatic carcinoma

SCF

Stem cell factor

siRNA

small interfering RNA

TTP

Time to progression

Notes

Acknowledgements

The authors would like to acknowledge the fundamental contribution of all the research collaborators and co-authors, which participated in the scientific studies concerning HSP expression and implications in canine spontaneous animal tumors.

References

  1. Acun, T., Doberstein, N., Habermann, J. K., et al. (2017). HLJ1 (DNAJB4) gene is a novel biomarker candidate in breast cancer. OMICS, 21, 257–265.PubMedCrossRefGoogle Scholar
  2. Argyle, D. J. (2009). Prostate cancer in dogs and men: A unique opportunity to study the disease. Veterinary Journal, 180, 137–138.CrossRefGoogle Scholar
  3. Asling, J., Morrison, J., & Mutsaers, A. J. (2016). Targeting HSP70 and GRP78 in canine osteosarcoma cells in combination with doxorubicin chemotherapy. Cell Stress & Chaperones, 21, 1065–1076.CrossRefGoogle Scholar
  4. Badowska-Kozakiewicz, A. M., & Malicka, E. (2012). Immunohistochemical evaluation of expression of heat shock proteins HSP70 and HSP90 in mammary gland neoplasms in bitches. Polish Journal of Veterinary Sciences, 15, 209–214.PubMedCrossRefGoogle Scholar
  5. Bagatell, R., Beliakoff, J., David, C. L., Marron, M. T., & Whitesell, L. (2005). Hsp90 inhibitors deplete key anti-apoptotic proteins in pediatric solid tumor cells and demonstrate synergistic anticancer activity with cisplatin. International Journal of Cancer, 113, 179–188.PubMedCrossRefGoogle Scholar
  6. Bagatell, R., Gore, L., Egorin, M. J., et al. (2007). Phase I pharmacokinetic and pharmacodynamic study of 17-N-allylamino-17-demethoxygeldanamycin in pediatric patients with recurrent or refractory solid tumors: A pediatric oncology experimental therapeutics investigators consortium study. Clinical Cancer Research, 15, 1783–1788.CrossRefGoogle Scholar
  7. Blackwood, L., Murphy, S., Buracco, P., et al. (2012). European consensus document on mast cell tumours in dogs and cats. Veterinary and Comparative Oncology, 10, e1–e29.PubMedCrossRefGoogle Scholar
  8. Bongiovanni, L., Romanucci, M., Fant, P., Lagadic, M., & Della Salda, L. (2008). Apoptosis and anti-apoptotic heat shock proteins in canine cutaneous infundibular keratinizing acanthomas and squamous cell carcinomas. Veterinary Dermatology, 19, 271–279.PubMedCrossRefGoogle Scholar
  9. Bongiovanni, L., Romanucci, M., Malatesta, D., D'Andrea, A., Ciccarelli, A., & Della Salda, L. (2015). Survivin and related proteins in canine mammary tumors: Immunohistochemical expression. Veterinary Pathology, 52, 269–275.PubMedCrossRefGoogle Scholar
  10. Calderwood, S. K., Gong, J., & Murshid, A. (2016). Extracellular HSPs: The complicated roles of extracellular hsps in immunity. Frontiers in Immunology, 7, 159.PubMedPubMedCentralGoogle Scholar
  11. Cappello, F., Rappa, F., David, S., Anzalone, R., & Zummo, G. (2003). Immunohistochemical evaluation of PCNA, p53, HSP60, HSP10 and MUC-2 presence and expression in prostate carcinogenesis. Anticancer Research, 23, 1325–1331.PubMedGoogle Scholar
  12. Carrasco, V., Canfrán, S., Rodríguez-Franco, F., Benito, A., Sáinz, A., & Rodríguez-Bertos, A. (2011). Canine gastric carcinoma: Immunohistochemical expression of cell cycle proteins (p53, p21, and p16) and heat shock proteins (Hsp27 and Hsp70). Veterinary Pathology, 48, 322–329.PubMedCrossRefGoogle Scholar
  13. Castilla, C., Congregado, B., Conde, J. M., et al. (2010). Immunohistochemical expression of Hsp60 correlates with tumor progression and hormone resistance in prostate cancer. Urology, 76, 1017.e1–1017.e6.CrossRefGoogle Scholar
  14. Chen, L., Li, J., Farah, E., et al. (2016). Cotargeting HSP90 and its client proteins for treatment of prostate cancer. Molecular Cancer Therapeutics, 15, 2107–2118.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Chi, K. N., Yu, E. Y., Jacobs, C., et al. (2016). A phase I dose-escalation study of apatorsen (OGX-427), an antisense inhibitor targeting heat shock protein 27 (Hsp27), in patients with castration-resistant prostate cancer and other advanced cancers. Annals of Oncology, 27, 1116–1122.PubMedCrossRefGoogle Scholar
  16. Chu, R. M., Sun, T. J., Yang, H. Y., et al. (2001). Heat shock proteins in canine transmissible venereal tumor. Veterinary Immunology and Immunopathology, 82, 9–21.PubMedCrossRefGoogle Scholar
  17. Ciocca, D. R., & Calderwood, S. K. (2005). Heat shock proteins in cancer: Diagnostic, prognostic, predictive, and treatment implications. Cell Stress & Chaperones, 10, 86–103.CrossRefGoogle Scholar
  18. Ciocca, D. R., Fanelli, M. A., Cuello-Carrion, F. D., & Castro, G. N. (2010). Heat shock proteins in prostate cancer: From tumorigenesis to the clinic. International Journal of Hyperthermia, 26, 737–747.PubMedCrossRefGoogle Scholar
  19. Clemente-Vicario, F., Alvarez, C. E., Rowell, J. L., et al. (2015). Human genetic relevance and potent antitumor activity of heat shock protein 90 inhibition in canine lung adenocarcinoma cell lines. PLoS One, 10, e0142007.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Cordonnier, T., Bishop, J. L., Shiota, M., et al. (2015). Hsp27 regulates EGF/β-catenin mediated epithelial to mesenchymal transition in prostate cancer. International Journal of Cancer, 136, E496–E507.PubMedCrossRefGoogle Scholar
  21. Cornford, P. A., Dodson, A. R., Parsons, K. F., et al. (2000). Heat shock protein expression independently predicts clinical outcome in prostate cancer. Cancer Research, 60, 7099–7105.PubMedGoogle Scholar
  22. Davidson, B., Valborg Reinertsen, K., Trinh, D., Reed, W., & Bøhler, P. J. (2016). BAG-1/SODD, HSP70, and HSP90 are potential prognostic markers of poor survival in node-negative breast carcinoma. Human Pathology, 54, 64–73.PubMedCrossRefGoogle Scholar
  23. Della Salda, L., & Romanucci, M. (2012). The role of heat shock proteins in mammary neoplasms: A brief review. Journal of Cancer Therapy, 3, 755–767.CrossRefGoogle Scholar
  24. Di Cerbo, A., Palmieri, B., De Vico, G., & Iannitti, T. (2014). Onco-epidemiology of domestic animals and targeted therapeutic attempts: Perspectives on human oncology. Journal of Cancer Research and Clinical Oncology, 140, 1807–1814.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Dong, L., Zhang, X., Ren, J., et al. (2013). Human prostate stem cell antigen and HSP70 fusion protein vaccine inhibits prostate stem cell antigen-expressing tumor growth in mice. Cancer Biotherapy & Radiopharmaceuticals, 28, 391–397.CrossRefGoogle Scholar
  26. Downing, S., Chien, M. B., Kass, P. H., Moore, P. E., & London, C. A. (2002). Prevalence and importance of internal tandem duplications in exons 11 and 12 of c-kit in mast cell tumors of dogs. American Journal of Veterinary Research, 63, 1718–1723.PubMedCrossRefGoogle Scholar
  27. Duffy, A., Le, J., Sausville, E., & Emadi, A. (2015). Autophagy modulation: A target for cancer treatment development. Cancer Chemotherapy and Pharmacology, 75, 439–447.PubMedCrossRefGoogle Scholar
  28. Eum, K. H., & Lee, M. (2011). Crosstalk between autophagy and apoptosis in the regulation of paclitaxel-induced cell death in v-Ha-ras-transformed fibroblasts. Molecular and Cellular Biochemistry, 348, 61–68.PubMedCrossRefGoogle Scholar
  29. Feldman, B. J., & Feldman, D. (2001). The development of androgen-independent prostate cancer. Nature Reviews Cancer, 1, 23–45.CrossRefGoogle Scholar
  30. Fenger, J. M., London, C. A., & Kisseberth, W. C. (2014). Canine osteosarcoma: A naturally occurring disease to inform pediatric oncology. ILAR Journal, 55, 69–85.PubMedCrossRefGoogle Scholar
  31. Foster, R. A. (2016). Male genital system. In M. G. Maxie (Ed.), Jubb, Kennedy, and Palmer’s pathology of domestic animals (Vol. 3, 6th ed., pp. 465–510). St. Louis: Elsevier.CrossRefGoogle Scholar
  32. Fu, W., Sharma, S. S., Ma, L., et al. (2013). Apoptosis of osteosarcoma cultures by the combination of the cyclin-dependent kinase inhibitor SCH727965 and a heat shock protein 90 inhibitor. Cell Death & Disease, 4, e566.CrossRefGoogle Scholar
  33. Fumo, G., Akin, C., Metcalfe, D. D., & Neckers, L. (2004). 17-Allylamino-17-demethoxygeldanamycin (17-AAG) is effective in down-regulating mutated, constitutively activated KIT protein in human mast cells. Blood, 103, 1078–1084.PubMedCrossRefGoogle Scholar
  34. Galli, S. J., Zsebo, K. M., & Geissler, E. N. (1994). The kit-ligand, stem-cell factor. Advances in Immunology, 55, 1–96.PubMedGoogle Scholar
  35. Gazitt, Y., Kolaparthi, V., Moncada, K., Thomas, C., & Freeman, J. (2009). Targeted therapy of human osteosarcoma with 17AAG or rapamycin: Characterization of induced apoptosis and inhibition of mTOR and Akt/MAPK/Wnt pathways. International Journal of Oncology, 34, 551–561.PubMedGoogle Scholar
  36. Ghioni, P., Bolognese, F., Duijf, P. H. G., van Bokhoven, H., Mantovani, R., & Guerrini, L. (2002). Complex transcriptional effects of p63 isoforms: Identification of novel activation and repression domains. Molecular and Cellular Biology, 22, 8659–8668.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Glaessgen, A., Jonmarker, S., Lindberg, A., et al. (2008). Heat shock proteins 27, 60 and 70 as prognostic markers of prostate cancer. APMIS, 116, 888–895.PubMedCrossRefGoogle Scholar
  38. Goldschmidt, M. H., Peña, L., & Zappulli, V. (2017). Tumors of the mammary gland. In D. J. Meuten (Ed.), Tumors in domestic animals (5th ed., pp. 723–765). Ames: Wiley.Google Scholar
  39. Gorska, M., Marino Gammazza, A., Zmijewski, M. A., et al. (2013). Geldanamycin-induced osteosarcoma cell death is associated with hyperacetylation and loss of mitochondrial pool of heat shock protein 60 (hsp60). PLoS One, 8, e71135.PubMedPubMedCentralCrossRefGoogle Scholar
  40. Gottlieb, R. A., & Carreira, R. S. (2010). Autophagy in health and disease, 5: Mitophagy as a way of life. American Journal of Physiology. Cell Physiology, 299, C203–C210.PubMedPubMedCentralCrossRefGoogle Scholar
  41. Grandér, D., & Panaretakis, T. (2010). Autophagy: Cancer therapy’s friend or foe? Future Medicinal Chemistry, 2, 285–297.PubMedCrossRefGoogle Scholar
  42. Hadzijusufovic, E., Rebuzzi, L., Gleixner, K. V., et al. (2008). Targeting of heat-shock protein 32/heme oxygenase-1 in canine mastocytoma cells is associated with reduced growth and induction of apoptosis. Experimental Hematology, 36, 1461–1470.PubMedCrossRefGoogle Scholar
  43. Hansen, R. K., Parra, I., Lemieux, P., Oesterreich, S., Hilsenbeck, S. G., & Fuqua, S. A. (1999). Hsp27 overexpression inhibits doxorubicin-induced apoptosis in human breast cancer cells. Breast Cancer Research and Treatment, 56, 187–196.PubMedCrossRefGoogle Scholar
  44. Hansen, R. K., Parra, I., Hilsenbeck, S. G., Himelstein, B., & Fuqua, S. A. W. (2001). Hsp27-induced MMp-9 expression is influenced by the Src tyrosine protein kinase yes. Biochemical and Biophysical Research Communications, 282, 186–193.PubMedCrossRefGoogle Scholar
  45. Heske, C. M., Mendoza, A., Edessa, L. D., et al. (2016). STA-8666, a novel HSP90 inhibitor/SN-38 drug conjugate, causes complete tumor regression in preclinical mouse models of pediatric sarcoma. Oncotarget, 7, 65540–65552.PubMedPubMedCentralCrossRefGoogle Scholar
  46. Hessenkemper, W., & Baniahmad, A. (2013). Targeting heat shock proteins in prostate cancer. Current Medicinal Chemistry, 20, 2731–2740.PubMedCrossRefGoogle Scholar
  47. Hsiao, Y. L., Hsieh, T. Z., Liou, C. J., et al. (2014). Characterization of protein marker expression, tumorigenicity, and doxorubicin chemoresistance in two new canine mammary tumor cell lines. BMC Veterinary Research, 10, 229.PubMedPubMedCentralCrossRefGoogle Scholar
  48. Hu, Y., Bobb, D., He, J., Hill, D. A., & Dome, J. S. (2015). The HSP90 inhibitor alvespimycin enhances the potency of telomerase inhibition by imetelstat in human osteosarcoma. Cancer Biology & Therapy, 16, 949–957.CrossRefGoogle Scholar
  49. Jagadish, N., Agarwal, S., Gupta, N., et al. (2016). Heat shock protein 70-2 (HSP70-2) overexpression in breast cancer. Journal of Experimental & Clinical Cancer Research, 35, 150.CrossRefGoogle Scholar
  50. Jhaveri, K., & Modi, S. (2015). Ganetespib: Research and clinical development. Onco Targets and Therapy, 8, 1849–1858.Google Scholar
  51. Jhaveri, K., Ochiana, S. O., Dunphy, M. P., et al. (2014). Heat shock protein 90 inhibitors in the treatment of cancer: Current status and future directions. Expert Opinion on Investigational Drugs, 23, 611–628.PubMedPubMedCentralCrossRefGoogle Scholar
  52. Kampinga, H. H., Hageman, J., Vos, M. J., et al. (2009). Guidelines for the nomenclature of the human heat shock proteins. Cell Stress & Chaperones, 14, 105–111.CrossRefGoogle Scholar
  53. Kang, G. H., Lee, E. J., Jang, K. T., et al. (2010). Expression of HSP90 in gastrointestinal stromal tumours and mesenchymal tumours. Histopathology, 56, 694–701.PubMedCrossRefGoogle Scholar
  54. Kim, K. H., Nelson, S. D., Kim, D. H., et al. (2012). Diagnostic relevance of overexpressions of PKC-θ and DOG-1 and KIT/PDGFRA gene mutations in extragastrointestinal stromal tumors: A Korean six-centers study of 28 cases. Anticancer Research, 32, 923–937.PubMedGoogle Scholar
  55. Kirkness, E. F., Bafna, V., Halpern, A. L., et al. (2003). The dog genome: Survey sequencing and comparative analysis. Science, 301, 1898–1903.PubMedCrossRefGoogle Scholar
  56. Kita, K., Shiota, M., Tanaka, M., et al. (2017). Hsp70 inhibitors suppress androgen receptor expression in LNCaP95 prostate cancer cells. Cancer Science, 108, 1820–1827.PubMedPubMedCentralCrossRefGoogle Scholar
  57. Kondo, R., Gleixner, K. V., Mayerhofer, M., et al. (2007). Identification of heat shock protein 32 (Hsp32) as a novel survival factor and therapeutic target in neoplastic mast cells. Blood, 110, 661–669.PubMedCrossRefGoogle Scholar
  58. Kumaraguruparan, R., Karunagaran, D., Balachandran, C., Murali Manohar, B., & Nagini, S. (2006). Of human and canines: A comparative evaluation of heat shock and apoptosis-associated proteins in mammary tumours. Clinica Chimica Acta, 365, 168–176.CrossRefGoogle Scholar
  59. Lemieux, P., Oesterreich, S., Lawrence, J. A., et al. (1997). The small heat shock protein Hsp27 increases invasiveness but decreases motility of breast cancer cells. Invasion & Metastasis, 17, 113–123.Google Scholar
  60. LeRoy, B., & Northrup, N. (2009). Prostate cancer in companion animals: Comparative and clinical aspects. Veterinary Journal, 180, 149–162.CrossRefGoogle Scholar
  61. Liang, W., Yang, C., Peng, J., Qian, Y., & Wang, Z. (2015). The expression of HSPD1, SCUBE3, CXCL14 and its relations with the prognosis in osteosarcoma. Cell Biochemistry and Biophysics, 73, 763–768.PubMedCrossRefGoogle Scholar
  62. Lianos, G. D., Alexiou, G. A., Mangano, A., et al. (2015). The role of heat shock proteins in cancer. Cancer Letters, 360, 114–118.PubMedCrossRefGoogle Scholar
  63. Lin, T. Y., Bear, M., Du, Z., et al. (2008). The novel HSP90 inhibitor STA-9090 exhibits activity against kit-dependent and -independent malignant mast cell tumors. Experimental Hematology, 36, 1266–1277.PubMedCrossRefGoogle Scholar
  64. Lin, T. Y., Fenger, J., Murahari, S., et al. (2010). AR-42, a novel HDAC inhibitor, exhibits biologic activity against malignant mast cell lines via down-regulation of constitutively activated kit. Blood, 115, 4217–4225.PubMedPubMedCentralCrossRefGoogle Scholar
  65. Lin, A. C., Liao, C. W., Lin, S. W., Huang, C. Y., Liou, C. J., & Lai, Y. S. (2015). Canine heat shock protein 27 promotes proliferation, migration, and doxorubicin resistance in the canine cell line DTK-F. Veterinary Journal, 205, 254–262.CrossRefGoogle Scholar
  66. Lindblad-Toh, K., Wade, C. M., Mikkelsen, T. S., et al. (2005). Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature, 438, 803–819.PubMedCrossRefGoogle Scholar
  67. London, C. A., Kisseberth, W. C., Galli, S. J., Geissler, E. N., & Helfand, S. C. (1996). Expression of stem cell factor receptor (c-kit) by the malignant mast cells from spontaneous canine mast cell tumours. Journal of Comparative Pathology, 115, 399–414.PubMedCrossRefGoogle Scholar
  68. London, C. A., Galli, S. J., Yuuki, T., Hu, Z. Q., Helfand, S. C., & Geissler, E. N. (1999). Spontaneous canine mast cell tumors express tandem duplications in the proto-oncogene c-kit. Experimental Hematology, 27, 689–697.PubMedCrossRefGoogle Scholar
  69. London, C. A., Bear, M. D., McCleese, J., et al. (2011). Phase I evaluation of STA-1474, a prodrug of the novel HSP90 inhibitor ganetespib, in dogs with spontaneous cancer. PLoS One, 6, e27018.PubMedPubMedCentralCrossRefGoogle Scholar
  70. Lu, S., Tan, Z., Wortman, M., Lu, S., & Dong, Z. (2010). Regulation of heat shock protein 70-1 expression by androgen receptor and its signaling in human prostate cancer cells. International Journal of Oncology, 36, 459–467.PubMedPubMedCentralCrossRefGoogle Scholar
  71. Ma, Y., Longley, B. J., Wang, X., Blount, J. L., Langley, K., & Caughey, G. H. (1999). Clustering of activating mutations in c-KIT’s juxtamembrane coding region in canine mast cell neoplasms. Journal of Investigative Dermatology, 112, 165–170.PubMedCrossRefGoogle Scholar
  72. Ma, W., Diep, K., Fritsche, H. A., Shore, N., & Albitar, M. (2014). Diagnostic and prognostic scoring system for prostate cancer using urine and plasma biomarkers. Genetic Testing and Molecular Biomarkers, 18, 156–163.PubMedCrossRefGoogle Scholar
  73. Macario, A. J., & Conway de Macario, E. (2007). Molecular chaperones: Multiple functions, pathologies, and potential applications. Frontiers in Bioscience, 12, 2588–2600.PubMedCrossRefGoogle Scholar
  74. Marconato, L., Frayssinet, P., Rouquet, N., et al. (2014). Randomized, placebo-controlled, double-blinded chemoimmunotherapy clinical trial in a pet dog model of diffuse large B-cell lymphoma. Clinical Cancer Research, 20, 668–677.PubMedCrossRefGoogle Scholar
  75. Marconato, L., Stefanello, D., Sabattini, S., et al. (2015). Enhanced therapeutic effect of APAVAC immunotherapy in combination with dose-intense chemotherapy in dogs with advanced indolent B-cell lymphoma. Vaccine, 33, 5080–5086.PubMedCrossRefGoogle Scholar
  76. Massimini, M., Palmieri, C., De Maria, R., et al. (2017). 17-AAG and apoptosis, autophagy, and mitophagy in canine osteosarcoma cell lines. Veterinary Pathology, 54, 405–412.PubMedCrossRefGoogle Scholar
  77. McCleese, J. K., Bear, M. D., Fossey, S. L., et al. (2009). The novel HSP90 inhibitor STA-1474 exhibits biologic activity against osteosarcoma cell lines. International Journal of Cancer, 125, 2792–2801.PubMedCrossRefGoogle Scholar
  78. Meschini, S., Condello, M., Lista, P., & Arancia, G. (2011). Autophagy: Molecular mechanisms and their implications for anticancer therapies. Current Cancer Drug Targets, 11, 357–379.PubMedCrossRefGoogle Scholar
  79. Miyake, H., Muramaki, M., Kurahashi, T., Yamanaka, K., Hara, I., & Fujisawa, M. (2006). Enhanced expression of heat shock protein 27 following neoadjuvant hormonal therapy is associated with poor clinical outcome in patients undergoing radical prostatectomy for prostate cancer. Anticancer Research, 26, 1583–1587.PubMedGoogle Scholar
  80. Miyake, H., Muramaki, M., Kurahashi, T., Takenaka, A., & Fujisawa, M. (2010). Expression of potential molecular markers in prostate cancer: Correlation with clinicopathological outcomes in patients undergoing radical prostatectomy. Urologic Oncology, 28, 145–151.PubMedCrossRefGoogle Scholar
  81. Moon, A., Bacchini, P., Bretoni, F., et al. (2010). Expression of heat shock proteins in osteosarcomas. Pathology, 42, 421–425.PubMedCrossRefGoogle Scholar
  82. Mori, M., Hitora, T., Nakamura, O., et al. (2015). Hsp90 inhibitor induces autophagy and apoptosis in osteosarcoma cells. International Journal of Oncology, 46, 47–54.PubMedCrossRefGoogle Scholar
  83. Mori, Y., Terauchi, R., Shirai, T., et al. (2017). Suppression of heat shock protein 70 by siRNA enhances the antitumor effects of cisplatin in cultured human osteosarcoma cells. Cell Stress & Chaperones, 22(5), 699706.CrossRefGoogle Scholar
  84. Morimoto, R. I. (1998). Regulation of the heat shock transcriptional response: Cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes & Development, 12, 3788–3796.CrossRefGoogle Scholar
  85. Mueller, F., Fuchs, B., & Kaser-Hotz, B. (2007). Comparative biology of human and canine osteosarcoma. Anticancer Research, 27, 155–164.PubMedGoogle Scholar
  86. Mühlenberg, T., Zhang, Y., Wagner, A. J., et al. (2009). Inhibitors of deacetylases suppress oncogenic KIT signaling, acetylate HSP90, and induce apoptosis in gastrointestinal stromal tumors. Cancer Research, 69, 6941–6950.PubMedPubMedCentralCrossRefGoogle Scholar
  87. Nolan, K. D., Kaur, J., & Isaacs, J. S. (2017). Secreted heat shock protein 90 promotes prostate cancer stem cell heterogeneity. Oncotarget, 8, 19323–19341.PubMedCrossRefGoogle Scholar
  88. Nollen, E. A. A., & Morimoto, R. I. (2002). Chaperoning signaling pathways: Molecular chaperones as stress-sensing ‘heat shock’ proteins. Journal of Cell Science, 115, 2809–2816.PubMedGoogle Scholar
  89. Oh, W. K., Galsky, M. D., Stadler, W. M., et al. (2011). Multicenter phase II trial of the heat shock protein 90 inhibitor, retaspimycin hydrochloride (IPI-504), in patients with castration-resistant prostate cancer. Urology, 78, 626–630.PubMedPubMedCentralCrossRefGoogle Scholar
  90. Okada, S., Furuya, M., Takenaka, S., et al. (2015). Localization of heat shock protein 110 in canine mammary gland tumors. Veterinary Immunology and Immunopathology, 167, 139–146.PubMedCrossRefGoogle Scholar
  91. Olson, P. N. (2007). Using the canine genome to cure cancer and other diseases. Theriogenology, 68, 378–381.PubMedCrossRefGoogle Scholar
  92. Oskay Halacli, S., Halacli, B., & Altundag, K. (2013). The significance of heat shock proteins in breast cancer therapy. Medical Oncology, 30, 575.PubMedCrossRefGoogle Scholar
  93. Ostrander, E. A., Giger, U., & Lindblad-Toh, K. (2006). The dog and its genome. New York: Cold Spring Harbor Laboratory.Google Scholar
  94. Ozger, H., Eralp, L., Atalar, A. C., et al. (2009). The effect of resistance-related proteins on the prognosis and survival of patients with osteosarcoma: An immunohistochemical analysis. Acta Orthopaedica et Traumatologica Turcica, 43, 28–34.PubMedCrossRefGoogle Scholar
  95. Palacios, C., Martín-Pérez, R., López-Pérez, A. I., Pandiella, A., & López-Rivas, A. (2010). Autophagy inhibition sensitizes multiple myeloma cells to 17-dimethylaminoethylamino-17-demethoxygeldanamycin-induced apoptosis. Leukemia Research, 34, 1533–1538.PubMedCrossRefGoogle Scholar
  96. Palmieri, C., Mancini, M., Benazzi, C., & Della Salda, L. (2014). Heat shock protein 90 is associated with hyperplasia and neoplastic transformation of canine prostatic epithelial cells. Journal of Comparative Pathology, 150, 393–398.PubMedCrossRefGoogle Scholar
  97. Park, J. S., Withers, S. S., Modiano, J. F., et al. (2016). Canine cancer immunotherapy studies: Linking mouse and human. Journal for ImmunoTherapy of Cancer, 4, 97.PubMedPubMedCentralCrossRefGoogle Scholar
  98. Patruno, R., Marech, I., Zizzo, N., et al. (2014). c-Kit expression, angiogenesis, and grading in canine mast cell tumour: A unique model to study c-Kit driven human malignancies. BioMed Research International, 2014, 730246.PubMedPubMedCentralCrossRefGoogle Scholar
  99. Ritossa, F. (1962). A new puffing pattern induced by temperature shock and DNP in drosophila. Experientia, 18, 571–573.CrossRefGoogle Scholar
  100. Riva, F., Brizzola, S., Stefanello, D., Crema, S., & Turin, L. (2005). A study of mutations in the c-kit gene of 32 dogs with mastocytoma. Journal of Veterinary Diagnostic Investigation, 17, 385–388.PubMedCrossRefGoogle Scholar
  101. Romanucci, M., Bongiovanni, L., Marruchella, G., et al. (2005). Heat shock proteins expression in canine intracutaneous cornifying epithelioma and squamous cell carcinoma. Veterinary Dermatology, 16, 108–116.PubMedCrossRefGoogle Scholar
  102. Romanucci, M., Marinelli, A., Sarli, G., & Della Salda, L. (2006). Heat shock protein expression in canine malignant mammary tumours. BMC Cancer, 6, 171.PubMedPubMedCentralCrossRefGoogle Scholar
  103. Romanucci, M., Bastow, T., & Della Salda, L. (2008). Heat shock proteins in animal neoplasms and human tumours-a comparison. Cell Stress & Chaperones, 13, 253–262.CrossRefGoogle Scholar
  104. Romanucci, M., D'Amato, G., Malatesta, D., et al. (2012a). Heat shock protein expression in canine osteosarcoma. Cell Stress & Chaperones, 17, 131–138.CrossRefGoogle Scholar
  105. Romanucci, M., Malatesta, D., Ciccarelli, A., et al. (2012b). Expression of heat shock proteins in premalignant and malignant urothelial lesions of bovine urinary bladder. Cell Stress & Chaperones, 17, 683–692.CrossRefGoogle Scholar
  106. Romanucci, M., Berardi, I., Ciccarelli, A., et al. (2013). Immunohistochemical evaluation of heat shock protein expression in normal canine nerve and peripheral nerve sheath tumours. Journal of Comparative Pathology, 149, 216–220.PubMedCrossRefGoogle Scholar
  107. Romanucci, M., Frattone, L., Ciccarelli, A., et al. (2016). Immunohistochemical expression of heat shock proteins, p63 and androgen receptor in benign prostatic hyperplasia and prostatic carcinoma in the dog. Veterinary and Comparative Oncology, 14, 337–349.PubMedCrossRefGoogle Scholar
  108. Romanucci, M., Massimini, M., Ciccarelli, A., et al. (2017). Hsp32 and Hsp90 immunoexpression, in relation to kit pattern, grading, and mitotic count in canine cutaneous mast cell tumors. Veterinary Pathology, 54, 222–225.PubMedCrossRefGoogle Scholar
  109. Rowell, J. L., McCarthy, D. O., & Alvarez, C. E. (2011). Dog models of naturally occurring cancer. Trends in Molecular Medicine, 17, 380–388.PubMedPubMedCentralCrossRefGoogle Scholar
  110. Rust, W., Kingsley, K., Petnicki, T., Padmanabhan, S., Carper, S. W., & Plopper, G. E. (1999). Heat shock protein 27 plays two distinct roles in controlling human breast cancer cell migration on laminin-5. Molecular Cell Biology Research Communications, 1, 196–202.PubMedCrossRefGoogle Scholar
  111. Selvarajah, G. T., Bonestroo, F. A., Kirpensteijn, J., et al. (2013). Heat shock protein expression analysis in canine osteosarcoma reveals HSP60 as a potentially relevant therapeutic target. Cell Stress & Chaperones, 18, 607–622.CrossRefGoogle Scholar
  112. Shevtsov, M., & Multhoff, G. (2016). Heat shock protein–peptide and HSP-based immunotherapies for the treatment of cancer. Frontiers in Immunology, 7, 171.PubMedPubMedCentralGoogle Scholar
  113. Signoretti, S., Waltregny, D., Dilks, J., et al. (2000). p63 is a prostate basal cell marker and is required for prostate development. The American Journal of Pathology, 157, 1769–1775.PubMedPubMedCentralCrossRefGoogle Scholar
  114. Switonski, M., Szczerbal, I., & Nowacka, J. (2004). The dog genome map and its use in mammalian comparative genomics. Journal of Applied Genetics, 45, 195–214.PubMedGoogle Scholar
  115. Szczubiał, M., Urban-Chmiel, R., & Łopuszyński, W. (2015). Heat shock protein 70 and nitric oxide concentrations in non-tumorous and neoplastic canine mammary tissues: Preliminary results-short communication. Acta Veterinaria Hungarica, 63, 209–214.PubMedCrossRefGoogle Scholar
  116. Talmadge, J. E., Singh, R. K., Fidler, I. J., & Raz, A. (2007). Murine models to evaluate novel and conventional therapeutic strategies for cancer. The American Journal of Pathology, 170, 793–804.PubMedPubMedCentralCrossRefGoogle Scholar
  117. Tatokoro, M., Koga, F., Yoshida, S., & Kihara, K. (2015). Heat shock protein 90 targeting therapy: State of the art and future perspective. EXCLI Journal, 14, 48–58.PubMedPubMedCentralGoogle Scholar
  118. Thakur, M. K., Heilbrun, L. K., Sheng, S., et al. (2016). A phase II trial of ganetespib, a heat shock protein 90 (Hsp90) inhibitor, in patients with docetaxel-pretreated metastatic castrate-resistant prostate cancer (CRPC)-a prostate cancer clinical trials consortium (PCCTC) study. Investigational New Drugs, 34, 112–118.PubMedCrossRefGoogle Scholar
  119. Tissieres, A., Mitchell, H. K., & Tracy, U. M. (1974). Protein synthesis in salivary glands of Drosophila melanogaster: Relation to chromosome puffs. Journal of Molecular Biology, 84, 389–398.PubMedCrossRefGoogle Scholar
  120. Tosti, G., Cocorocchio, E., Pennacchioli, E., Ferrucci, P. F., Testori, A., & Martinoli, C. (2014). Heat-shock proteins-based immunotherapy for advanced melanoma in the era of target therapies and immunomodulating agents. Expert Opinion on Biological Therapy, 14, 955–967.PubMedCrossRefGoogle Scholar
  121. Trepel, J., Mollapour, M., Giaccone, G., & Neckers, L. (2010). Targeting the dynamic Hsp90 complex in cancer. Nature Reviews Cancer, 10, 537–549.PubMedCrossRefGoogle Scholar
  122. Trieb, K., Lechleitner, T., Lang, S., Windhager, R., Kotz, R., & Dirnhofer, S. (1998). Heat shock protein 72 expression in osteosarcoma correlates with good response to neoadjuvant chemotherapy. Human Pathology, 29, 1050–1055.PubMedCrossRefGoogle Scholar
  123. Trieb, K., Lang, S., & Kotz, R. (2000). Heat-shock protein72 in human osteosarcoma: T-lymphocyte reactivity and cytotoxicity. Pediatric Hematology and Oncology, 17, 355–364.PubMedCrossRefGoogle Scholar
  124. Uozaki, H., Ishida, T., Kakiuchi, C., et al. (2000). Expression of heat shock proteins in osteosarcoma and its relationship to prognosis. Pathology, Research and Practice, 196, 665–673.PubMedCrossRefGoogle Scholar
  125. Wang, H., Lu, M., Yao, M., & Zhu, W. (2016). Effects of treatment with an Hsp90 inhibitor in tumors based on 15 phase II clinical trials. Molecular and Clinical Oncology, 5, 326–334.PubMedPubMedCentralCrossRefGoogle Scholar
  126. Welle, M. M., Bley, C. R., Howard, J., & Rüfenacht, S. (2008). Canine mast cell tumours: A review of the pathogenesis, clinical features, pathology and treatment. Veterinary Dermatology, 19, 321–339.PubMedCrossRefGoogle Scholar
  127. Whiteside, T. L., Demaria, S., Rodriguez-Ruiz, M. E., Zarour, H. M., & Melero, I. (2016). Emerging opportunities and challenges in cancer immunotherapy. Clinical Cancer Research, 22, 1845–1855.PubMedPubMedCentralCrossRefGoogle Scholar
  128. Wu, G., Osada, M., Guo, Z., et al. (2005). ΔNp63α up-regulates the Hsp70 gene in human cancer. Cancer Research, 65, 758–766.PubMedGoogle Scholar
  129. Wu, J., Liu, T., Rios, Z., Mei, Q., Lin, X., & Cao, S. (2017). Heat shock proteins and cancer. Trends in Pharmacological Sciences, 38, 226–256.PubMedCrossRefGoogle Scholar
  130. Xu, C., Liu, J., Hsu, L. C., Luo, Y., Xiang, R., & Chuang, T. H. (2011). Functional interaction of heat shock protein 90 and Beclin 1 modulates toll-like receptor-mediated autophagy. The FASEB Journal, 25, 2700–2710.PubMedPubMedCentralCrossRefGoogle Scholar
  131. Xu, L., Woodward, C., Dai, J., & Prakash, C. (2013). Metabolism and excretion of 6-chloro-9-(4-methoxy-3,5-dimethylpyridin-2-ylmethyl)-9H-purin-2-ylamine, an HSP90 inhibitor, in rats and dogs and assessment of its metabolic profile in plasma of humans. Drug Metabolism and Disposition, 41, 2133–2147.PubMedCrossRefGoogle Scholar
  132. Yan, L., Zhang, W., Zhang, B., Xuan, C., & Wang, D. (2017). BIIB021: A novel inhibitor to heat shock protein 90-addicted oncology. Tumour Biology, 39, 1010428317698355.PubMedGoogle Scholar
  133. Yang, Z., Chee, C. E., & Huang, S. (2011). The role of autophagy in cancer: Therapeutic implications. Molecular Cancer Therapeutics, 10, 1533–1541.PubMedPubMedCentralCrossRefGoogle Scholar
  134. Zemke, D., Yamini, B., & Yuzbasiyan-Gurkan, V. (2002). Mutations in the juxtamembrane domain of c-KIT are associated with higher grade mast cell tumors in dogs. Veterinary Pathology, 39, 529–535.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Veterinary Pathology Unit, Faculty of Veterinary MedicineUniversity of TeramoTeramoItaly

Personalised recommendations