Ståhle-Bäckdahl M, Parks W C
Department of Dermatology, Karolinska Hospital, Stockholm, Sweden.
Am J Pathol. 1993 Apr;142(4):995-1000.
Tumor invasion and metastasis are assisted by multiple proteinases that degrade basement membrane and stromal matrix components. We used in situ hybridization with 35S-labeled RNA probes and immunohistochemistry to localize cellular sites of 92-kd gelatinase production in sections of invasive squamous cell carcinoma. Signal for enzyme messenger RNA was detected only in numerous eosinophils that surrounded the tumor nodules, and immunohistochemical staining verified the presence of enzyme protein in these granulocytes and also revealed strong reactivity in neutrophils. No resident or other migratory cell type was positive for gelatinase messenger RNA or protein, and no signal was detected by either assay in samples of healthy skin. These data indicate that eosinophils have the capacity to synthesize actively 92-kd gelatinase, whereas neutrophils store and probably release the enzyme on demand. Because of the capacity of 92-kd gelatinase to degrade both basement membrane and interstitial extracellular matrix molecules, the expression, delivery, and secretion of this metalloproteinase by granulocytes may be critical for tumor invasion.
肿瘤侵袭和转移由多种降解基底膜和基质成分的蛋白酶介导。我们采用35S标记的RNA探针原位杂交和免疫组化方法，在浸润性鳞状细胞癌切片中定位92-kd明胶酶的细胞产生部位。仅在肿瘤结节周围的大量嗜酸性粒细胞中检测到酶信使RNA信号，免疫组化染色证实这些粒细胞中存在酶蛋白，并且在中性粒细胞中也显示出强反应性。没有常驻细胞或其他游走细胞类型对明胶酶信使RNA或蛋白呈阳性，在健康皮肤样本中两种检测方法均未检测到信号。这些数据表明嗜酸性粒细胞具有主动合成92-kd明胶酶的能力，而中性粒细胞储存并可能根据需要释放该酶。由于92-kd明胶酶具有降解基底膜和间质细胞外基质分子的能力，粒细胞对这种金属蛋白酶的表达、传递和分泌可能对肿瘤侵袭至关重要。
