Induction of resistance to murine tumor development is associated with alterations in the glycosylation of blood serum proteins

Abstract

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 growthstimulating 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 timedependent 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.

Cure of Mice with Advanced Ovarian Adenocarcinoma CaO1 by the Serum Blood Proteins

“…Hence, the tumor-bearing host constantly produces a serum factor that is necessary for the growth of the tumor. The existence of such a factor can explain the features of tumor recurrence and metastasis [1,5,6,9]. Why this factor still not identified?…”

Tumor-Specific Blood Serum Factors as Basis of Tumor Dormancy

“…Interestingly, the increase of mitotic activity is in direct relation to the quantity of the removed tumor-cell bearing ascitic fluid. Removal of 1.5 ml ascitic fluid caused an increase of the mitotic index from 15% to 30%, and removal of 5-6 ml to 80% [4,5]. These dramatic increases of mitotic activities can only be observed 24 hrs after tumor removal.…”

“…Clues for the existence of such a feedback mechanism come from experiments showing that mice generate more immune cells (blood leukocytes, peritoneal cells, and spleen cells) 7 hrs after the removal of ascitic fluid. Interestingly, injection of these cell types into healthy mice leads to resistance of these animals towards tumor development [4,5]. Since this phenomenon cannot be observed by other experimental interventions (e.g.…”

Quantitative Regulation of Melanoma Growth in the Host by Tumor-Specific Serpins in Blood Serum is a Main Reason for Inefficient Tumor Treatment

“…PBLC, SLC, or PC were injected into mice, and Ehrlich tumor cells were inoculated 14 days later (see the scheme in Figure 8) (taken from Donenko et al, 2009 with permission).…”