title: Induction of resistance to murine tumor development is associated with alterations in the glycosylation of blood serum proteins.
abstract: The phenomenon of accelerated metastatic tumor growth following the removal of the primary tumor is a major reason for cancer relapse, caused by underlying mechanisms that are not as yet understood. We hypothesized that a growth-stimulating factor is produced by the tumor-bearing host. This assumption was confirmed by an experiment involving the removal of a primary tumor (ascitic and solid Ehrlich carcinoma cells) from C57B1/6 mice, after which accelerated proliferation was observed in the remaining tumor cells. Peripheral blood leukocytes (PBLCs), spleen leukocytes (SLCs) and peritoneal cells (PCs) were transferred from donor animals with their tumors removed to healthy animals, along with tumor cells. This procedure suppressed tumor growth in 20-40% of the recipient animals when PBLCs, SLCs or PCs were collected 6-8 h after the removal of the tumor. In a second experiment, PBLCs, SLCs or PCs were injected into the mice, and the tumor cells were inoculated 14 days later. Resistance to tumor development occurred within the same time frame (6-8 h) but was more pronounced (60-80%) than in the previous experiment. Ehrlich carcinoma cells affected the binding of FITC-labeled blood serum glycoproteins in a time-dependent manner. Mass spectrometry revealed that the spectrum of glycopeptides in blood serum taken from control mice differed from the spectra of glycopeptides obtained from mice 8-24 h after the removal of Ehrlich carcinoma cells. Comparable effects were also observed with Cloudman S91 melanoma. In conclusion, the inhibition of tumor growth mediated by donor cells (PBLCs, SLCs and PCs) transferred from operated donor animals to recipient animals indicates the existence of a tumor-regulating factor in blood serum. This phenomenon is associated with characteristic alterations in the glycosylation of blood serum proteins.
authors.affiliation: N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, Moscow 115478, Russia. fedor.donenko@gmail.com.
authors.forename: F V
authors.initials: FV
authors.lastname: Donenko
authors.forename: R K
authors.initials: RK
authors.lastname: Ziganshin
authors.forename: S M
authors.initials: SM
authors.lastname: Sitdikova
authors.forename: B S
authors.initials: BS
authors.lastname: Amandzholov
authors.forename: M V
authors.initials: MV
authors.lastname: Kiselevskii
authors.forename: T
authors.initials: T
authors.lastname: Efferth