Crosstalk between mast cells and pancreatic cancer cells contributes to pancreatic tumor progression.
Crosstalk between mast cells and pancreatic cancer cells contributes to pancreatic tumor progression.
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DOI：
10.1158/1078-0432.ccr-09-1230
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发表时间：
2010-04-15
期刊：
影响因子：
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通讯作者：
Bentrem DJ
中科院分区：
文献类型：
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作者：
Strouch MJ;Cheon EC;Salabat MR;Krantz SB;Gounaris E;Melstrom LG;Dangi-Garimella S;Wang E;Munshi HG;Khazaie K;Bentrem DJ
目的：探讨肥大细胞在胰腺癌中的临床和病理意义，以及肥大细胞与肿瘤细胞之间的相互作用。应用免疫组织化学方法检测53例胰腺癌组织中类胰蛋白酶的表达。肥大细胞计数与临床变量和生存期相关。将癌症患者和良性胰腺疾病患者的血清类胰蛋白酶活性进行比较。体外观察胰腺癌条件培养液对肥大细胞迁移的影响。用胸腺嘧啶核苷掺入法评价人肥大细胞株LAD-2的条件培养液对肿瘤和正常导管细胞增殖的影响。用Matrigel侵袭实验评估肥大细胞条件培养液在存在和不存在基质金属蛋白酶抑制剂GM6001的情况下对癌细胞侵袭的影响。胰腺癌组织中肥大细胞的浸润率明显高于正常胰腺组织[(11.4±6.7)vs.2.0±1.4(p<；0.001)]。浸润性肥大细胞增多与较高级别的肿瘤(P<；0.0001)和较差的存活率相关。胰腺癌患者血清类胰蛋白酶活性升高(p<；0.05)。在体外，AsPC1和PANC-1细胞诱导肥大细胞迁移。肥大细胞条件培养液可诱导胰腺癌细胞迁移、增殖和侵袭，但对正常导管细胞无影响。此外，肥大细胞对癌细胞侵袭的影响在很大程度上是依赖于基质金属蛋白酶的。肿瘤浸润性肥大细胞与胰腺癌预后不良相关。在体外，肥大细胞和胰腺癌细胞之间的相互作用促进了肿瘤的生长和侵袭。
To assess the clinical and pathological significance of mast cell infiltration in human pancreatic cancer and evaluate crosstalk between mast cells and cancer cells in vitro. Immunohistochemistry for tryptase was performed on 53 pancreatic cancer specimens. Mast cell counts were correlated with clinical variables and survival. Serum tryptase activity from cancer patients was compared to patients with benign pancreatic disease. In vitro, the effect of pancreatic cancer conditioned media on mast cell migration was assessed. The effect of conditioned media from the human mast cell line, LAD-2, on cancer and normal ductal cell proliferation was assessed by thymidine incorporation. Matrigel invasion assays were used to evaluate the effect of mast cell conditioned media on cancer cell invasion in the presence and absence of a matrix metalloproteinase inhibitor, GM6001. Mast cell infiltration was significantly increased in pancreatic cancer compared to normal pancreatic tissue [11.4±6.7vs.2.0±1.4(p<0.001)]. Increased infiltrating mast cells correlated with higher grade tumors (p<0.0001) and worse survival. Patients with pancreatic cancer had elevated serum tryptase activity (p<0.05). In vitro, AsPC1 and PANC-1 cells induced mast cell migration. Mast cell conditioned media induced pancreatic cancer cell migration, proliferation and invasion but had no effect on normal ductal cells. Furthermore, the effect of mast cells on cancer cell invasion was in large part MMP-dependent. Tumor infiltrating mast cells are associated with worse prognosis in pancreatic cancer. In vitro, the interaction between mast cells and pancreatic cancer cells promote tumor growth and invasion.