Kaur Kawaljit, Chang Hui-Hua, Cook Jessica, Eibl Guido, Jewett Anahid
Division of Oral Biology and Oral Medicine, School of Dentistry and Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
Front Immunol. 2017 Dec 4;8:1606. doi: 10.3389/fimmu.2017.01606. eCollection 2017.
The aim of our studies is to determine the dynamics of natural killer (NK) cell modulation in gingivae in precancerous and cancerous stages of pancreatic and oral cancers in P48+/Cre;LSL-KRASG12D (KC) mice carrying a pancreas-specific oncogenic Kras mutation and BLT-humanized mice. Wild type and KC mice fed with control diet (CD) or high-fat calorie diet (HFCD), and the pancreatic and oral tumor-bearing humanized BLT (hu-BLT) mice were used to determine precancerous and cancer induced changes in numbers and function of gingival NK cells. Increased numbers of PanIN lesions and the greatest score of inflammation in pancreas of KC mice fed with CD and HFCD co-related with significant decline in percentages of circulating and gingival NK cells, lack of DX5+ NK expansion and increased secretion of IFN-γ and IL-6 after culture. At the malignant stage of pancreatic cancer, hu-BLT tumor-bearing mice had the lowest secretion of IFN-γ from cells dissociated from the gingival tissues as compared to those from non-tumor-bearing mice. Injection of NK cells into tumor-bearing mice increased IFN-γ secretion, and the secretion was similar or higher than those obtained by gingival cells from non-tumor-bearing hu-BLT control mice. The highest increase in IFN-γ secretion was observed when tumor-bearing mice were fed with AJ2 probiotic bacteria and injected with the NK cells. Along with an increase in secretion of IFN-γ, injection of NK cells in the presence and absence of feeding with AJ2 in pancreatic tumor-bearing mice increased percentages of CD45+ and CD3+ T cells in oral gingival cells. Similar results were observed with oral tumors. In conclusion, these results indicated that oral cavity may mirror systemic disease and provide a rationale for why cancer patients may be prone to suffer from diverse oral pathologies.
我们研究的目的是确定在携带胰腺特异性致癌Kras突变的P48+/Cre;LSL-KRASG12D（KC）小鼠和BLT人源化小鼠中，胰腺癌和口腔癌癌前和癌变阶段牙龈中自然杀伤（NK）细胞调节的动态变化。使用喂食对照饮食（CD）或高脂高热量饮食（HFCD）的野生型和KC小鼠，以及携带胰腺和口腔肿瘤的人源化BLT（hu-BLT）小鼠，来确定癌前和癌症诱导的牙龈NK细胞数量和功能变化。喂食CD和HFCD的KC小鼠胰腺中PanIN病变数量增加且炎症评分最高，这与循环和牙龈NK细胞百分比显著下降、DX5+ NK细胞缺乏扩增以及培养后IFN-γ和IL-6分泌增加相关。在胰腺癌的恶性阶段，与未携带肿瘤的小鼠相比，携带hu-BLT肿瘤的小鼠牙龈组织中分离出的细胞分泌的IFN-γ最低。向携带肿瘤的小鼠注射NK细胞可增加IFN-γ分泌，且该分泌与未携带肿瘤的hu-BLT对照小鼠牙龈细胞所获得的分泌相似或更高。当携带肿瘤的小鼠喂食AJ2益生菌并注射NK细胞时，观察到IFN-γ分泌增加最多。在有或没有喂食AJ2的情况下，向携带胰腺肿瘤的小鼠注射NK细胞，除了增加IFN-γ分泌外，还增加了口腔牙龈细胞中CD45+和CD3+ T细胞的百分比。口腔肿瘤也观察到类似结果。总之，这些结果表明口腔可能反映全身性疾病，并为癌症患者为何可能易患多种口腔疾病提供了理论依据。
