Tumor-Specific Blood Serum Factors as Basis of Tumor Dormancy


  • Fedor V. Donenko N.N. Blokhin Russian Cancer Research Center
  • Natalia G. Kormosh N.N. Blokhin Russian Cancer Research Center
  • Thomas Efferth Johannes Gutenberg University
  • Michail V. Kiselevski N.N. Blokhin Russian Cancer Research Center




Anti-proteases, Ehrlich carcinoma, Proteases, Serpins, Serum proteins, Tumor growth, tumor dormancy


In the present review, we focus on the importance of blood serum factors for tumor growth in vivo. Data from mice experiments indicate the existence of serum factors, which decrease the dormancy of Ehrlich carcinoma cells from 85 to 20%. The impaired production of these factors increases the life span of tumor-bearing animals from 14 days to 120 days. Blocking the production of tumor-specific factors causes the complete regression of already developed Ehrlich carcinoma. These serum factors do not affect the malignant carcinoma cells in vitro. We identified serpins as tumor dormancy serum factors. Experimental evidence suggests that serpins are not only essential for tumor growth. Serpins are also involved in the regeneration of normal tissues, such as adipose tissue, recurrence after cosmetic operations (liposuction), inhibiting rejection after liver transplantation, protection of parasitic flat worms living in host tissues and organs etc. We conclude that the inhibition of serum dormancy factor may represent attractive novel strategies for the prevention and treatment of relapsed cancers.

Author Biography

Thomas Efferth, Johannes Gutenberg University

Department of Pharmaceutical Biology


[1] Gunduz N, Fisher B, Saffer EA. Effect of surgical removal on the growth and kinetics of residual tumor. Cancer Res 1979; 39: 3861-5.
[2] Fisher B, Gunduz N, Coyle J, Rudock C, Saffer E. Presence of a growth-stimulating factor in serum following primary tumor removal in mice. Cancer Res 1989; 49: 1996-2001.
[3] Goldin A, Kline I and Sofina ZP, Eds. Experimental Evaluation. National Cancer Institute Monograph 55. NIH Publication no.1933. U.S. Department of Health and Human Services. National Institutes of Health, NCI, Bethesda, Maryland 1980.
[4] Donenko FV, Ziganshin RK, Sitdikova SM, Amandzholov BS, Kiselevskii MV, et al. Induction of resistance to murine tumor development is associated with alterations in the glycosylation of blood serum proteins. Mol Med Rep 2009; 2: 487-95. doi: 10.3892/mmr_00000126.
[5] Donenko FV, Sitdikova SM, Syrtsev AV, Gradyushko AT, Kiselevsky MV, et al. Hemoglobin-associated proteins isolated from blood serum of Ehrlich carcinoma-bearing mice. Int J Oncol 2008; 32: 885-93. DOI: 10.3892/ijo.32.4.885
[6] Sitdikova SM, Amandzholov BS, Serebryakova MV, Zhdanovich MJ, Kiselevsky MV, et al. Peculiarities of hemoglobin interaction with serum proteins of mice with Ehrlich carcinoma. Bull Exp Biol Med. 2006; 141: 624-7. http://dx.doi.org/10.1007/s10517-006-0237-6
[7] Donenko FV, Sitdikova SM, Amandzholov BS, Kiselevsky MV. Biological activity of hemoglobin-containing complex isolated from blood serum of mice with Ehrlich carcinoma. Bull Exp Biol Med 2006; 142: 347-50. http://dx.doi.org/10.1007/s10517-006-0363-1
[8] Donenko FV, Ziganshin RH, Anisimova NY, Voyushin KE, Sitdikova SM, et al. Identification of serpin (alpha-1-antitrypsin) as serum growth inhibitory factor in murine ehrlich carcinoma by proteomics. Cancer Genom Proteom 2010; 7: 147-56.
[9] Donenko FV, Kiselevskii MV, Efferth T. Quantitative Regulation of Melanoma Growth in the Host by Tumor-Specific Serpins in Blood Serum is a Main Reason for Inefficient Tumor Treatment In: Tanaka Yohei editors. Breakthroughs in melanoma research Intechweb.org 2011; ISBN 978-953-307-291-3, Ch. 24; p. 509-32. DOI: 10.5772/20910.
[10] Miller HR, Pemberton AD. Tissue-specific expression of mast cell granule serine proteinases and their role in inflammation in the lung and gut. Immunology 2002; 105: 375-90. http://dx.doi.org/10.1046/j.1365-2567.2002.01375.x
[11] Trishin AV, Zhdanovich MIu, Savvateeva LV, Toptygin AIu, Donenko FV, et al. Associated synthesis of some secreted pathogenicity factors of Klebsiella pneumoniae. Vestn Ross Akad Med Nauk 2005; 9: 43-8.
[12] Liu XQ, Hu ZQ, Pei YF, Tao R. Clinical operational tolerance in liver transplantation: state-of-the-art perspective and future prospects. Hepatobiliary Pancreat Dis Int 2013; 12: 12-33. http://dx.doi.org/10.1016/S1499-3872(13)60002-8
[13] Yan Y, Liu S, Song G, Xu Y, Dissous C. Characterization of novel vaccine candidate and serine proteinase inhibitor from Schistosoma japonicum (Sj serpin). Vet Parasitol 2005; 131: 53-60. http://dx.doi.org/10.1016/j.vetpar.2005.04.038
[14] Babayeva AG. Immunologichesky mechanisms of regulation of regenerative processes. Moscow: Medicine 1972; p. 160.
[15] Ginat DT, Bhatt S, Dogra VS. Replacement lipomatosis of the kidney: sonographic features. J Ultrasound Med 2008; 27: 1393-5.
[16] Puttarajappa C, Dhoble A. Mediastinal lipomatosis as a cause of low voltage complexes on electrocardiogram and widened mediastinum: A case report. Case J 2008; 1: 171. http://dx.doi.org/10.1186/1757-1626-1-171
[17] Jowett C, Mitra P, O'Donnell P, Singh DS. Synovial lipomatosis of hind foot tendon sheaths: case reports and literature review. Foot Ankle Int 2008; 29: 752-5. http://dx.doi.org/10.3113/FAI.2008.0752
[18] Pandzi Jaksi V, Bozkov V. From ancient enigmas to novel paradigms: a depiction of multiple symmetric lipomatosis. Coll Antropol 2008; 32: 637-40.
[19] Goshtasby P, Brooks G, Fielding LP. Lipomatous disorder of the peri-trochanteric soft tissue: case report and review. Curr Surg 2006; 63: 338-44. http://dx.doi.org/10.1016/j.cursur.2006.03.005
[20] Gorelik E. Concomitant tumour immunity and the resistance to a second tumor challenge. Adv Cancer Res 1983; 39: 71-120. http://dx.doi.org/10.1016/S0065-230X(08)61033-7
[21] Kallenbach LR, Johnson KL, Bianchi DW. Fetal cell microchimerism and cancer: a nexus of reproduction, immunology, and tumor biology. Cancer Res 2011; 71: 8-12. http://dx.doi.org/10.1158/0008-5472.CAN-10-0618
[22] Miech RP. The role of fetal microchimerism in autoimmune disease. Int J Clin Exp Med 2010; 3: 164-8