Expression and secretion of neuroleukin/phosphohexose isomerase/maturation factor as autocrine motility factor by tumor cells.
Expression and secretion of neuroleukin/phosphohexose isomerase/maturation factor as autocrine motility factor by tumor cells.
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发表时间：
1998-06
期刊：
影响因子：
11.2
通讯作者：
Y. Niinaka;Sandor Paku;A. Haga;Hideomi Watanabe;Avraham Raz
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作者：
Y. Niinaka;Sandor Paku;A. Haga;Hideomi Watanabe;Avraham Raz
片段化蛋白质微测序获得的结果表明，自分泌运动因子（AMF）是一种肿瘤分泌的Mr 55,000细胞因子，可调节体外细胞运动以及体内侵袭和转移，是神经白细胞介素（NLK）/磷酸己糖异构酶（PHI）/成熟因子（MF）多肽。在这里，我们克隆、测序并研究了 AMF/NLK/PHI/MF 在肿瘤细胞及其正常对应细胞中的表达、分泌和分布。尽管正常细胞和肿瘤细胞都表达该基因产物，但仅在肿瘤细胞中观察到与该蛋白选择性分泌相关的过度表达。在人类癌症和正常细胞中发现的 AMF/NLK/PHI/MF 的 cDNA 序列是相同的，这表明肿瘤细胞的分泌与突变或可变剪接无关。免疫组织化学可视化显示 AMF/NLK/PHI/MF 定位于管状囊泡中，广泛分布在整个细胞质中，并且不与任何特定的细胞骨架网络共定位。共焦显微成像显示 AMF 与其受体（Mr 78,000 糖蛋白）之间存在部分共定位，特别是在恶性细胞表面外围。结果表明，细胞外AMF活性可能是前体多肽细胞内裂解的结果，该前体多肽被肿瘤细胞过度表达并通过非经典分泌机制选择性分泌。
The results obtained from fragmented protein microsequencing have suggested that autocrine motility factor (AMF), a tumor-secreted Mr 55,000 cytokine that regulates cell motility in vitro as well as invasion and metastasis in vivo, is the neuroleukin (NLK)/phosphohexose isomerase (PHI)/maturation factor (MF) polypeptide. Here, we cloned, sequenced, and studied the expression, secretion, and distribution of AMF/NLK/PHI/MF in neoplastic and their normal counterpart cells. Although both normal and neoplastic cells express the gene product, overexpression associated with selective secretion of the protein was observed only in tumor cells. The cDNA sequences of AMF/NLK/PHI/MF found in both human cancer and normal cells were found to be identical, suggesting that its secretion by neoplastic cells is independent of mutation or alternative splicing. Immunohistochemical visualization has depicted AMF/NLK/PHI/MF to be localized into tubular-like vesicles, diffusely distributed throughout the cytoplasm and not colocalized with any particular cytoskeletal network. Confocal microscopic imaging had shown a partial colocalization between AMF and its receptor (Mr 78,000 glycoprotein), especially on the malignant cell surface periphery. The results suggest that extracellular AMF activity may be a result of the product of intracellular cleavage of a precursor polypeptide, which is overexpressed and selectively secreted through a nonclassical secretory mechanism by neoplastic cells.