Denver Health Medical Center, 777 Bannock Street, Denver, CO 80204-0206, USA.
J Gastrointest Surg. 2010 Oct;14(10):1560-5. doi: 10.1007/s11605-010-1329-1. Epub 2010 Sep 11.
Perioperative blood transfusion has been linked to decreased survival for pancreas cancer. Noting clinical data associating female blood products with increased morbidity, our lab has demonstrated that transfusion of female blood augments metastatic events compared to male blood in an immunocompetent murine pancreatic cancer model. It has been suggested that tumor-associated macrophages correlate with tumor progression by promoting angiogenesis. More recently, tumor-associated neutrophils have been implicated in aggressive tumor behavior. We hypothesize that differences in gender-specific transfusion-mediated pancreatic cancer progression are due to microenvironmental changes within the tumor. To test this hypothesis, we examined tumor-associated neutrophils and macrophage ratios in male and female mice with pancreatic cancer receiving blood transfusion from male or female donors.
C57/BL6 mice, age 7-9 weeks, underwent splenic inoculation with 2.5 × 10(5) PanO2 murine pancreatic adenocarcinoma cells. Mice were transfused on post-op day 7 with 1 ml/kg supernatant from day 42 male or female packed red cells. Necropsy was performed at 5 weeks or earlier for clinical deterioration, and tumors harvested. Frozen sections (5 µm) were stained for neutrophils and macrophages by immunofluorescence. Data were analyzed using ANOVA; p ≤ 0.05 was used to determine significance; N ≥ 3 per group.
Clinically, male mice had greater morbidity and mortality than female mice when receiving female blood products, with roughened hair coat, development of ascites and death due to bowel obstruction. In evaluating the tumor microenvironment from mice receiving female blood products, male mice were noted to have a greater neutrophil to macrophage ratio than female mice, 0.176 ± 0.028 vs. 0.073 ± 0.012, p = 0.03. When examining neutrophil to macrophage ratio in mice receiving male blood products, no difference was noted (p = 0.48).
Male mice with pancreas cancer have greater morbidity than female mice when receiving female blood products. Furthermore, the difference in neutrophil to macrophage ratio suggests that gender-specific blood transfusion promotes aggressive tumor behavior in male mice via microenvironmental changes. These data warrant further study to delineate sex-related differences in pancreatic cancer progression.
围手术期输血与胰腺癌患者生存率降低有关。我们实验室注意到与女性血液制品相关的临床数据会增加发病率，已经证明与男性血液相比，在免疫功能正常的胰腺癌细胞模型中输注女性血液会增加转移事件。有人提出，肿瘤相关巨噬细胞通过促进血管生成与肿瘤进展相关。最近，肿瘤相关中性粒细胞也被牵连到侵袭性肿瘤行为中。我们假设，性别特异性输血介导的胰腺癌进展的差异是由于肿瘤内微环境的变化。为了验证这一假设，我们检查了接受来自男性或女性供体输血的患有胰腺癌的雄性和雌性小鼠中的肿瘤相关中性粒细胞和巨噬细胞的比例。
C57/BL6 小鼠，年龄 7-9 周，接受 2.5×10(5) PanO2 胰腺腺癌细胞的脾内接种。在术后第 7 天，用 1ml/kg 来自第 42 天的男性或女性浓缩红细胞上清液进行输血。对于临床恶化的情况，在 5 周或更早进行尸检，并收获肿瘤。通过免疫荧光对冷冻切片（5 µm）进行中性粒细胞和巨噬细胞染色。使用 ANOVA 分析数据；p≤0.05 用于确定显著性；每组 n≥3。
临床上，当接受女性血液制品时，雄性小鼠比雌性小鼠发病率和死亡率更高，表现为毛发粗糙、腹水形成和因肠梗阻而死亡。在评估接受女性血液制品的小鼠的肿瘤微环境时，与雌性小鼠相比，雄性小鼠的中性粒细胞与巨噬细胞的比值更大，为 0.176±0.028 比 0.073±0.012，p=0.03。当检查接受男性血液制品的小鼠的中性粒细胞与巨噬细胞的比值时，没有差异（p=0.48）。
当接受女性血液制品时，患有胰腺癌的雄性小鼠比雌性小鼠发病率更高。此外，中性粒细胞与巨噬细胞比值的差异表明，性别特异性输血通过微环境变化促进雄性小鼠的侵袭性肿瘤行为。这些数据需要进一步研究以阐明胰腺癌进展中的性别相关差异。
