Rat mammary carcinoma cells secrete active collagenase and activate latent enzyme in the stroma via plasminogen activator
Rat mammary carcinoma cells secrete active collagenase and activate latent enzyme in the stroma via plasminogen activator
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大鼠乳腺癌细胞分泌活性胶原酶并通过纤溶酶原激活剂激活基质中的潜在酶
DOI：
10.1002/ijc.2910280418
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发表时间：
1981
影响因子：
6.4
通讯作者：
R. Stephens
中科院分区：
文献类型：
--
作者：
R. O'Grady;Linda I. Upfold;R. Stephens
对近交系雌性大鼠自发性乳腺腺癌(AC)中性蛋白酶的分泌进行了研究。来自肿瘤的肿瘤上皮细胞培养产生一种酶，该酶符合特定胶原酶的标准。与非肿瘤细胞培养相比，肿瘤胶原酶是一种活性酶，因为用胰酶或对氨基苯基汞(APMA)处理不能提高活性。肿瘤细胞也大量产生纤溶酶原激活物(PA)。地塞米松(Dex)(10−6M)可显著降低上述两种酶的水平。加入纤溶酶和纤溶酶原激活抑制剂氨甲环酸(TA)不影响胶原酶活性，即使在10−1M TA时也不影响胶原酶活性，也不积累潜在胶原酶。新生大鼠肺成纤维细胞在培养中可分泌潜伏性胶原酶。这种潜伏性酶可被肿瘤细胞培养液和纤溶酶原激活，但这种作用被TA抑制。这些结果表明，肿瘤细胞本身分泌胶原酶作为一种活性酶。PA也是分泌的，与肿瘤胶原酶无关，但在纤溶酶原存在的情况下，能够激活由肿瘤内或周围组织中的非肿瘤细胞产生的潜在胶原酶。这种肿瘤在体外具有很强的胶原蛋白溶解能力，这可能是其在体内快速侵袭的部分原因。
A spontaneous mammary adenocarcinoma (AC) from an inbred female rat was investigated with regard to secretion of neutral proteases. Cultures of neoplastic epithelial cells derived from the tumour secreted an enzyme that fulfilled the criteria for a specific collagenase. In contrast to cultures of non‐neoplastic cells, tumour collagenase was present as an active enzyme, since treatment with trypsin or p‐aminophenylmercuric acetate (APMA) did not increase activity. The neoplastic cells were also prolific producers of plasminogen activator (PA). Dexamethasone (Dex) (10−6M) markedly reduced the levels of both enzymes. Addition of tranexamic acid (TA), an inhibitor of plasmin and of plasminogen activation, did not affect collagenase activity, even at 10−1M TA, nor did latent collagenase accumulate. Latent collagenase was secreted in culture by normal fibroblasts from neonatal rat lungs. This latent enzyme was activated by the addition of tumour cell medium plus plasminogen, but this effect was inhibited by the addition of TA. These results demonstrate that the neoplastic cells themselves secrete collagenase as an active enzyme. PA is also secreted, is not involved with tumour collagenase, but is capable, in the presence of plasminogen, of activating latent collagenase produced by the non‐neoplastic cells within the tumour or in the surrounding tissue. This tumour possesses potent collagenolytic ability in vitro which may be partly responsible for its rapid invasion in vivo.