Cataltepe S, Gornstein E R, Schick C, Kamachi Y, Chatson K, Fries J, Silverman G A, Upton M P
Division of Newborn Medicine, Children's Hospital, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115-5737, USA.
J Histochem Cytochem. 2000 Jan;48(1):113-22. doi: 10.1177/002215540004800112.
Squamous cell carcinoma antigen (SCCA) serves as a serological marker for advanced squamous cell carcinomas (SCCs) and as an indicator of therapeutic response. Recent molecular studies show that the SCCA is transcribed by two almost identical tandemly arrayed genes, SCCA1 and SCCA2. These genes are members of the high molecular weight serine proteinase inhibitor (serpin) superfamily. Although SCCA1 and SCCA2 are 92% identical at the amino acid level, they have distinct biochemical properties. Paradoxically, SCCA1 is an inhibitor of papain-like cysteine proteinases, such as cathepsins L, S, and K, whereas SCCA2 inhibits chymotrypsin-like serine proteinases, cathepsin G, and mast cell chymase. Using a new set of discriminatory monoclonal antibodies (MAbs) and polymerase chain reaction (PCR) assay, we showed that SCCA1 and SCCA2 were co-expressed in the suprabasal layers of the stratified squamous epithelium of the tongue, tonsil, esophagus, uterine cervix and vagina, Hassall's corpuscles of the thymus, and some areas of the skin. SCCA1 and SCCA2 also were detected in the pseudo-stratified columnar epithelium of the conducting airways. Examination of squamous cell carcinomas of the lung and head and neck showed that SCCA1 and SCCA2 were co-expressed in moderately and well-differentiated tumors. Moreover, there was no differential expression between these SCCA "isoforms" in normal or malignant tissues. In contrast to previous studies, these data indicated that the expression of SCCA1 and SCCA2 was not restricted to the squamous epithelium and that these serpins may coordinately regulate cysteine and serine proteinase activity in both normal and transformed tissues.
鳞状细胞癌抗原（SCCA）是晚期鳞状细胞癌（SCC）的血清学标志物及治疗反应指标。近期分子研究表明，SCCA由两个几乎完全相同的串联排列基因SCCA1和SCCA2转录而成。这些基因是高分子量丝氨酸蛋白酶抑制剂（丝氨酸蛋白酶抑制剂）超家族的成员。尽管SCCA1和SCCA2在氨基酸水平上有92%的同一性，但它们具有不同的生化特性。矛盾的是，SCCA1是木瓜蛋白酶样半胱氨酸蛋白酶（如组织蛋白酶L、S和K）的抑制剂，而SCCA2抑制胰凝乳蛋白酶样丝氨酸蛋白酶、组织蛋白酶G和肥大细胞糜酶。使用一组新的鉴别性单克隆抗体（MAb）和聚合酶链反应（PCR）检测方法，我们发现SCCA1和SCCA2在舌、扁桃体、食管、子宫颈和阴道的复层鳞状上皮的基底上层、胸腺的哈氏小体以及皮肤的某些区域共表达。在传导气道的假复层柱状上皮中也检测到了SCCA1和SCCA2。对肺癌及头颈部鳞状细胞癌的检查显示，SCCA1和SCCA2在中度和高分化肿瘤中共同表达。此外，在正常或恶性组织中，这些SCCA“异构体”之间没有差异表达。与先前的研究不同，这些数据表明SCCA1和SCCA2的表达并不局限于鳞状上皮，并且这些丝氨酸蛋白酶抑制剂可能在正常组织和转化组织中协同调节半胱氨酸和丝氨酸蛋白酶的活性。
