Investigation of stam cells in experimental salivary gland carcinogenesis. (Immunohistochemical evaruation for oncogene product)

在DMBA海绵颗粒致癌和结扎大鼠颌下腺的实验过程中，观察了增殖细胞及其免疫组织化学特性。正常大鼠颌下腺的增殖细胞很少，表皮生长因子定位于颗粒曲管的颗粒内，颗粒曲管、纹状管和排泄管的柱状和过渡细胞表达S-100α，角蛋白K8.12、碱性成纤维细胞生长因子和癌基因c-erbB-2在SD和ED中表达。DmBA/海绵植入2~3周后，在坏死性水肿区可见少量增殖细胞，坏死性水肿性…周围可见管状结构和扩张的导管段，少量增殖细胞(10~25%)。更大的面积。K8.12角蛋白、S-100α蛋白、碱性成纤维细胞生长因子和c-erb B-2癌蛋白表达阳性，EGF表达阴性。植入DMBA/海绵后4~6周，角化上皮在DMBA/海绵周围呈囊状延伸，在囊性上皮的基底部和基底部可见一些增殖细胞(*27%)。囊性上皮的组织学和免疫组织化学特征与口腔白斑相似，c-erbB-2癌基因蛋白阳性表达。DMBA/海绵植入后8~12周出现鳞状细胞癌(SCC)。增殖细胞主要位于鳞状细胞癌的基底区和基底区，增殖率达30%以上。12周后可见肿瘤细胞浸润性生长特征，基底膜断裂，结扎管状结构的SMG中，增殖细胞增多，在实验的第3天，增殖细胞核抗原标记的峰值约为50%，之后逐渐下降至实验第21天的10%。结扎胆管的SMG的组织学和免疫组织化学结果与癌变过程中出现的胆管样结构相似。在实验动物未结扎的腺体中，腺泡细胞表现出增殖活性，在实验第2天达到高峰(*20%)，在实验第10天迅速下降到正常水平。这一结果表明，在SMG分泌功能加速的情况下，分泌细胞可能在功能适应方面出现增殖。然而，在受损的情况下，导管段具有更多的增殖潜力，这些细胞可能是腺体再生过程中的主要参与细胞，并可能参与大多数唾液腺肿瘤的组织发生。此外，c-erb B-2癌蛋白在导管段和肿瘤细胞中的表达，以及EGF在GCT中的积聚，这些发现可能影响了相对于其他器官的快速癌变。较少

Proliferating cells and its immunohistochemical properties were evaluated during experimental carcinogenesis induced by DMBA containing sponge-pellet implantation and after duct-ligation of rat submandibular glands (SMGs).In the normal rat SMGs, proliferating cells were very very few, epidermal growth factor (EGF) was confined to the granules in granular convoluted tubules (GCTs), S-100 alpha was found in pillar and transition cells in GCT and striated duct (SD) and excretory duct (ED), K8.12 keratin, basic fibroblast growth factor (bFGF), and c-erbB-2 oncoprotein were found in SD and ED,and laminin existed at basement membrane of glandular epithelia and blood vessels.Two to three weeks after DMBA/sponge implantation, small clusters of proliferating cells were observed in necrotic oedematous area surrounding DMBA/sponge and duct-like structures and dilated ductal segments with small numbers of proliferating cells (10-25%) were found in inflammatory area surrounding necrotic oedematous … More area. These components showed positive for K8.12 keratin, S-100 alpha protein, bFGF,and c-erbB-2 oncoprotein and negative for EGF.Four to six week after DMBA/sponge implantation, keratinized epithelium extended surrounding DMBA/sponge like a cyst and some proliferating cells were observed in basal and parabasal area of cystic epithelium (* 27%). Histological and immunohistochemical features of cystic epithelium were similar to those of oral leucoplakias and c-erbB-2 oncoprotein was observed in this lesion. Squamous cell carcinomas (SCC) arose 8 to 12 weeks after DMBA/sponge implantation. Proliferating cells were observed mainly in basal and parabasal area of SCC and the frequency of proliferating cells were more than 30%. C-erbB-2 oncoprotein was observed also in the SCC.Invasive growth feature of tumor cells with breakages of basement membrane were some times found in after 12 weeks speciments.In the duct-ligated SMG,proliferating cells were increased in duct-like structures and the peak of the PCNA labeling was about 50% at the third day and then gradually decreased into 10% at the 21st day of experiment. Histological and immunohistochemical findings of duct-like structures in duct-ligated SMG were similar to those of duct-like structures which appeared during carcinogenesis. In unligated gland of experimental animals showed proliferation activity in acinar cells and its peak was at the second day (* 20%) and rapidly decrease into normal level at the 10th day of experiment.These results suggested that in case of acceleration of secretory function of SMG,secretory cells may proliferate as for the functional adaptation. However, in case of damage, ductal segments have more potential for proliferation and these cells may be the major participant cells during glandular regeneration and possibly source in the histogenesis of the majority of salivary gland tumors. Furthermore, apperance of c-erbB-2 oncoprotein in ductal segment and tumor cells, and EGF is accumulated in GCT,these findings may influences of rapidly carcinogenesis compared to another organs. Less