Intravenous delivery of the plasma fraction of stored packed erythrocytes promotes pancreatic cancer growth in immunocompetent mice

Abstract

BACKGROUND: Perioperative blood transfusion in pancreatic cancer patients has been linked to decreased survival; however, a causal mechanism has not been determined. During the processing and storage of packed erythrocytes, biologically active molecules accumulated in the acellular plasma fraction; therefore, the authors hypothesized that the plasma fraction of stored packed erythrocytes promoted tumor progression. METHODS: Proliferation and migration of murine pancreatic cancer and control cells were determined in vitro in response to the plasma fraction from leukocyte and nonleukocyte-reduced fresh versus stored packed erythrocytes. Last, an immunocompetent murine model was used to assess the effect of the plasma fraction of stored and processed packed erythrocytes on pancreatic cancer progression. RESULTS: Incubation of pancreatic cancer cells with the plasma fraction of packed erythrocytes increased proliferation and migration. Intravenous delivery of the acellular plasma fraction to mice with pancreatic cancer significantly increased the tumor weight in both leukocyte-reduced and nonleukocyte-reduced packed-erythrocyte groups (P < .01), although tumor growth and morbidity were greatest in the nonleukocytereduced group. CONCLUSIONS: The plasma fraction of stored packed erythrocytes promoted murine pancreatic cancer proliferation and migration in vitro and when administered intravenously, significantly augmented pancreatic cancer growth in immunocompetent mice. Cancer 2010;116:3862-74.

Impact of Allogenic and Autologous Transfusion on Immune Function in Patients with Tumors

“…The results of this study also showed that the CD3 + , CD4 + , CD4 + /CD8 + ratio and NK cells in allogeneic blood transfusion group began to decline immediately after operation and had not recovered on postoperative day 7, indicating that allogeneic blood transfusion can reduce postoperative T lymphocyte subsets and NK cells number of tumor patients thus allogeneic blood transfusion can reduce cellular immune function. By observing impact of allogeneic blood transfusion on immune function in gastric cancer patients, Maeta et al found that allogeneic blood transfusion can significantly reduce the number of NK cells in gastric cancer patients, leading to inhibition of patients' cellular immune function (Barnett et al, 2010). Our study result is basically consistent with the study result of Maeta.…”

Perioperative Blood Transfusions Promote Pancreas Cancer Progression

“…The model has the advantage of using syngeneic mice and controlling for tumor inoculum (250,000 cells per mouse), transfusion volume (the equivalent of the acellular fraction of pRBCs that a patient would receive with a 2U transfusion, and controlled and relatively minor operative stress. This model revealed marked augmentation of tumor growth and increased lymph node metastasis in vivo compared with animals with tumor, but without transfusion [29]. Interestingly, these results were independent of blood storage time, indicating the presence of bioactive substances that can promote tumor growth may be present in plasma after only 1 d of storage and that lipid mediators may not be causative for pancreas tumor progression in these mice, although mice receiving older blood did develop more ascites.…”

“…Therefore, preclinical models may offer great opportunities to control for many of these variables and study the effects of transfusion-related immunomodulation (TRIM) on tumor biology in pancreatic adenocarcinoma. Based on the work of Silliman et al [16,17] showing the accumulation of lipid mediators in the acellular fraction of stored pRBCs, the authors have recently demonstrated that this acellular fraction increases tumor cell proliferation and migration in an in vitro model of murine pancreatic adenocarcinoma [29]. These findings led to the intravenous injection of the acellular fraction of pRBCs in immuncompetent mice that previously had been inoculated with Pan02 cancer cells.…”

Activation state of stromal inflammatory cells in murine metastatic pancreatic adenocarcinoma

“…With this preclinical model, we are able to control for many variables, such as tumor burden and genetic variability that make clinical research difficult (3). Pancreatic adenocarcinoma continues to be a disease of high morbidity and mortality (1,20), with a propensity of metastases, even with small primary tumors (21).…”