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邓宁R-3327大鼠前列腺腺癌模型中细胞迁移和黏附的转移潜能及底物依赖性

Metastatic potential and substrate dependence of cell motility and attachment in the Dunning R-3327 rat prostatic adenocarcinoma model.

作者信息

Mohler J L, Levy F, Sharief Y

机构信息

Department of Surgery (Division of Urology), University of North Carolina, Chapel Hill 27599-7235.

出版信息

Cancer Res. 1991 Dec 15;51(24):6580-5.

PMID:1742730
Abstract

Cancer cell motility has been associated with metastatic potential of sublines of the Dunning R-3227 rat prostatic adenocarcinoma model. However, three sublines of high motility lacked the capacity for metastasis. In all previous works, motility has been studied upon plastic and only upon attached cells at least 18 h after gravity plating. We studied two highly motile sublines; MAT-LyLu metastasizes to lungs and lymph nodes whereas PIF-1 metastasizes rarely. We compared the motility and attachment capability of cells from the Dunning model in serum-free media upon plastic, glass, laminin, type IV collagen, fibronectin, and elastin to determine whether study upon more physiological surfaces could better explain the discrepancy in metastatic capability observed in vivo. In the high-motility low-metastatic PIF-1 and high-motility high-metastatic MAT-Lylu sublines, membrane ruffling, pseudopodal extension, and cellular translation upon plastic in serum-free media were reduced (P less than 0.0001) by 33 and 31, 70 and 60, and 77 and 65%, respectively. When returned to serum-containing media, biological characteristics (histology, chromosomal number, growth rate, host survival, and metastatic potential) were unchanged. Motility was affected by substrate (analysis of variance, P less than 0.05); however, no consistent pattern of enhancement or detriment occurred in any substrate across both sublines. When motility was compared between sublines, membrane ruffling and cellular translation were relatively unaffected by substrate, whereas pseudopodal extension was altered significantly by different substrates. However, upon individual substrates, no significant differences in motility existed between the two sublines to resolve the inconsistency of high-motility but low-metastatic potential in the PIF-1 subline. Therefore, we examined cell attachment, since in order for a metastatic cell to be motile upon substrate, it must first attach to it. Percentage of 10(5) cells attached was determined in serum-free media with the use of a cell counter after 1, 2, 4, 8, and 16 h on plastic and plastic coated with laminin, fibronectin, elastin, or type IV collagen. Cell attachment increased with time (P less than 0.05) on all substrates for MAT-LyLu (r = 0.95) and PIF-1 (r = 0.98). Attachment of MAT-LyLu cells was impaired by fibronectin and enhanced by elastin, laminin, and type IV collagen compared to plastic at all time points.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

癌细胞的运动性与Dunning R - 3227大鼠前列腺腺癌模型亚系的转移潜能相关。然而,三个高运动性亚系缺乏转移能力。在以往所有研究中,运动性仅在塑料表面且至少在重力接种18小时后附着的细胞上进行研究。我们研究了两个高运动性亚系;MAT - LyLu可转移至肺和淋巴结,而PIF - 1很少发生转移。我们比较了Dunning模型细胞在无血清培养基中于塑料、玻璃、层粘连蛋白、IV型胶原、纤连蛋白和弹性蛋白上的运动性和附着能力,以确定在更接近生理状态的表面上进行研究是否能更好地解释体内观察到的转移能力差异。在高运动性低转移的PIF - 1和高运动性高转移的MAT - Lylu亚系中,无血清培养基中塑料表面上的膜皱襞形成、伪足延伸和细胞迁移分别减少了33%和31%、70%和60%、77%和65%(P < 0.0001)。当恢复到含血清培养基时,生物学特性(组织学、染色体数目、生长速率、宿主存活和转移潜能)未改变。运动性受底物影响(方差分析,P < 0.05);然而,在两个亚系的任何底物上均未出现一致的增强或减弱模式。当比较亚系之间的运动性时,膜皱襞形成和细胞迁移相对不受底物影响,而伪足延伸则因不同底物而显著改变。然而,在单个底物上,两个亚系之间的运动性无显著差异,无法解释PIF - 1亚系高运动性但低转移潜能的不一致性。因此,我们检查了细胞附着情况,因为转移性细胞要在底物上运动,必须首先附着于其上。在无血清培养基中,使用细胞计数器在塑料以及涂有层粘连蛋白、纤连蛋白、弹性蛋白或IV型胶原的塑料上分别培养1、2、4、8和16小时后,测定10⁵个细胞的附着百分比。对于MAT - LyLu(r = 0.95)和PIF - 1(r = 0.98),在所有底物上细胞附着均随时间增加(P < 0.05)。与塑料相比,在所有时间点,纤连蛋白会损害MAT - LyLu细胞的附着,而弹性蛋白、层粘连蛋白和IV型胶原则会增强其附着。(摘要截断于400字)

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