Kobayashi M, Hamada J, Li Y Q, Shinobu N, Imamura M, Okada F, Takeichi N, Hosokawa M
Laboratory of Pathology, Hokkaido University School of Medicine, Sapporo.
Jpn J Cancer Res. 1995 Mar;86(3):298-303. doi: 10.1111/j.1349-7006.1995.tb03054.x.
Production of metalloproteinases such as collagenases has been reported to be involved in the metastasis of cancer cells. Granulocytic sarcoma in extramedullary sites can be formed by similar steps to other cancers. In this study, we have examined the secretion of type IV collagenases and a tissue inhibitor of metalloproteinase-1 (TIMP-1) in several human leukemia cell lines, including a granulocytic sarcoma-derived cell line established from a patient with granulocytic sarcomas in dermal tissues. We have also examined the invasive capacity of these leukemia cell lines into reconstituted basement membrane, Matrigel, which was used for in vitro invasion assay. Among the human leukemia cell lines used in this study, only the granulocytic sarcoma cell line was found to secrete type IV collagenase constitutively. Other myeloid leukemia cell lines such as HL-60 and U-937 produced type IV collagenase only after treatment with 12-O-tetradecanoylphorbol-13-acetate. All the cell lines secreted similar amounts of the tissue inhibitor of metalloproteinases. In vitro invasion assay revealed that the granulocytic sarcoma cell line showed higher invasive capacity than the other cell lines. These results suggest that the secretion of 92 kDa type IV collagenase plays a role in the leukemia cells' invasion of extramedullary tissues.
据报道，诸如胶原酶等金属蛋白酶的产生与癌细胞转移有关。髓外部位的粒细胞肉瘤可通过与其他癌症相似的步骤形成。在本研究中，我们检测了几种人白血病细胞系中IV型胶原酶和金属蛋白酶组织抑制剂-1（TIMP-1）的分泌情况，其中包括从一名患有皮肤组织粒细胞肉瘤的患者建立的粒细胞肉瘤衍生细胞系。我们还检测了这些白血病细胞系对重组基底膜基质胶的侵袭能力，基质胶用于体外侵袭试验。在本研究使用的人白血病细胞系中，仅发现粒细胞肉瘤细胞系组成性分泌IV型胶原酶。其他髓系白血病细胞系如HL-60和U-937仅在经12-O-十四酰佛波醇-13-乙酸酯处理后才产生IV型胶原酶。所有细胞系分泌的金属蛋白酶组织抑制剂量相似。体外侵袭试验显示，粒细胞肉瘤细胞系的侵袭能力高于其他细胞系。这些结果表明，92 kDa IV型胶原酶的分泌在白血病细胞侵袭髓外组织中起作用。
