Tumor-Specific Blood Serum Factors as Basis of Tumor Dormancy

Abstract

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.

Conformational changes in inter-α-trypsin inhibitor heavy chain 4 activate its tumor-specific activity in mice with B16 melanoma

“…A previous study by our group demonstrated changes in the glycosylation of serum proteins in tumor-bearing mice (1). However, it was not possible to establish a link between the various N-linked oligosaccharide residues and the tumors of animals or cancer patients (1)(2)(3). Another previous study by our group showed that the serpin α-anti-trypsin from blood serum inhibits or blocks the growth of tumors (4).…”

“…The question that arises from these studies is how proteins in the blood serum of tumor-bearing mice as well as in the blood serum of tumor-free mice acquire tumor-associated biological activity. It is known that the blood serum of tumor-bearing animals contains a certain factor which specifically accelerates tumor growth (2,5). However, all attempts to identify this factor as a novel protein in the blood serum of tumor-bearing animals were unsuccessful (5,6).…”

“…Serpin, unlike albumin, is a glycosylated protein and its spatial structure changes due to glycosylation, not due to internal cross-links. Glycosylation-induced changes of blood serum proteins during tumor growth are discussed above (2).…”