Heidtmann H H, Salge U, Havemann K, Kirschke H, Wiederanders B
Philipps-University, Department of Internal Medicine, Marburg, Germany.
Oncol Res. 1993;5(10-11):441-51.
Secretion of pro-cathepsin L, the precursor of a lysosomal cysteine proteinase, has been described for ras-transfected mouse fibroblasts and several human cancer cell lines. The secretion of a latent but stable precursor might be a means for tumor cells to involve this proteinase in extracellular matrix breakdown. Since lung cancer is the leading cause of cancer death in the industrialized countries, we therefore studied the secretion of pro-cathepsin L in 11 human non-small cell lung cancer cell lines (EPLC 32M1, NCI H157, EPLC 272H, U1752, LCLC 103H, LCLC 97TM1, U 1810, NCI H661, NCI H23, NCI H125, and NCI H596) and 8 human small cell lung cancer cell lines (SCLC 22H, NCI H60, NCI H82, NCI H526, NCI H146, NCI H841, NCI H510, and DMS 79). Immunoblot analysis of cell conditioned media showed that latent pro-cathepsin L (M(r) 42 kDa) was secreted in all 11 non-small cell lung cancer cell lines. Three of these cell lines secreted an additional inactive form of cathepsin L of M(r) 24 kDa. In contrast, the 8 small cell lung cancer cell lines did not secrete any detectable cathepsin L-immunoreactive material. Phorbol-12-myristate-13-acetate increased the secretion of pro-cathepsin L in 6 of the non-small cell lung cancer cell lines. The cathepsin L precursor could be activated in vitro at pH 3, accompanied by a shift in molecular mass to 34 kDa. Chicken egg white cystatin prevented the acid activation. Specific antibodies against a synthetic peptide from the pro-sequence of cathepsin L reacted with the nonsmall cell lung cancer cathepsin L precursor. Extracellular pro-cathepsin L may be important in the tumor biology of non-small cell lung cancer and would be a good target for novel diagnostic and therapeutic approaches, since the majority of physiological lysosomal proteinases are contained in intracellular compartments only.
溶酶体半胱氨酸蛋白酶组织蛋白酶L的前体——组织蛋白酶原L的分泌，已在经ras转染的小鼠成纤维细胞和几种人类癌细胞系中被描述。分泌一种潜在但稳定的前体可能是肿瘤细胞使这种蛋白酶参与细胞外基质降解的一种方式。由于肺癌是工业化国家癌症死亡的主要原因，因此我们研究了11种人类非小细胞肺癌细胞系（EPLC 32M1、NCI H157、EPLC 272H、U1752、LCLC 103H、LCLC 97TM1、U 1810、NCI H661、NCI H23、NCI H125和NCI H596）以及8种人类小细胞肺癌细胞系（SCLC 22H、NCI H60、NCI H82、NCI H526、NCI H146、NCI H841、NCI H510和DMS 79）中组织蛋白酶原L的分泌情况。对细胞条件培养基进行免疫印迹分析表明，所有11种非小细胞肺癌细胞系均分泌潜在的组织蛋白酶原L（相对分子质量42 kDa）。其中3种细胞系还分泌了另一种相对分子质量24 kDa的无活性组织蛋白酶L形式。相比之下，8种小细胞肺癌细胞系均未分泌任何可检测到的组织蛋白酶L免疫反应性物质。佛波醇-12-肉豆蔻酸酯-13-乙酸酯增加了6种非小细胞肺癌细胞系中组织蛋白酶原L的分泌。组织蛋白酶L前体在体外pH 3时可被激活，同时相对分子质量转变为34 kDa。鸡卵清半胱氨酸蛋白酶抑制剂可阻止酸激活。针对组织蛋白酶L前序列的合成肽的特异性抗体与非小细胞肺癌组织蛋白酶L前体发生反应。细胞外组织蛋白酶原L在非小细胞肺癌的肿瘤生物学中可能很重要，并且由于大多数生理性溶酶体蛋白酶仅存在于细胞内区室中，因此它将是新型诊断和治疗方法的良好靶点。
