Turpeenniemi-Hujanen T, Thorgeirsson U P, Hart I R, Grant S S, Liotta L A
J Natl Cancer Inst. 1985 Jul;75(1):99-103.
Expression of a basement membrane collagen-degrading metalloprotease activity (collagenase IV) was studied in a series of murine cell hybrids derived from fusions between highly metastatic cells (B16-F10RR) or moderately metastatic cells (UV-2237RR) and tumorigenic cells (K-1735 clone 16) or normal cells [peritoneal macrophages (PEC) or C3H mouse embryo fibroblasts (C3H-F)]. The collagenase IV activity of the parent cells and the hybrids was assayed in vitro and compared to the metastatic propensity of the same cells evaluated in both syngeneic (C57BL/6 X C3H/HeN)F1 mice and BALB/c nude mice. The level of collagenase IV activity secreted by the parent lines correlated with their metastatic capacity. The highly metastatic B16-F10RR line secreted the highest enzyme activity, whereas the tumorigenic but nonmetastatic K-1735 clone 16 and the normal parents PEC and C3H-F secreted the lowest enzyme activity. The enzyme activity was completely inhibited with EDTA. The hybrid derived from fusion of cells from two metastatic cell lines as well as hybrids derived from a metastatic and a nonmetastatic tumor cell line expressed higher levels of collagenase IV activity than either parent, and this expression was associated with a high ability to produce metastases in both nude and syngeneic mice. Fusion of metastatic cells with normal cells produced hybrid cells that exhibited suppression of both collagenase IV activity and metastatic capacity. Collagenase IV activity and metastatic propensity can, therefore, be altered by somatic cell hybridization; in the series of hybrids examined in these experiments the expression of type IV collagen-degrading metalloprotease activity and the metastatic ability were closely correlated, which suggests that collagenase IV activity and other properties required for metastasis are genetically linked.
在一系列小鼠细胞杂种中研究了一种基底膜胶原降解金属蛋白酶活性（胶原酶IV）的表达情况。这些杂种细胞来源于高转移性细胞（B16 - F10RR）或中度转移性细胞（UV - 2237RR）与致瘤细胞（K - 1735克隆16）或正常细胞[腹膜巨噬细胞（PEC）或C3H小鼠胚胎成纤维细胞（C3H - F）]之间的融合。在体外测定亲代细胞和杂种细胞的胶原酶IV活性，并将其与在同基因（C57BL / 6×C3H / HeN）F1小鼠和BALB / c裸鼠中评估的相同细胞的转移倾向进行比较。亲代细胞系分泌的胶原酶IV活性水平与其转移能力相关。高转移性的B16 - F10RR系分泌的酶活性最高，而致瘤但无转移能力的K - 1735克隆16以及正常亲代PEC和C3H - F分泌的酶活性最低。该酶活性被EDTA完全抑制。来自两个转移性细胞系的细胞融合产生的杂种以及来自转移性和非转移性肿瘤细胞系的杂种表达的胶原酶IV活性水平高于任何一个亲代，并且这种表达与在裸鼠和同基因小鼠中产生转移的高能力相关。转移性细胞与正常细胞融合产生的杂种细胞表现出胶原酶IV活性和转移能力均受到抑制。因此，胶原酶IV活性和转移倾向可通过体细胞杂交改变；在这些实验中检测的一系列杂种中，IV型胶原降解金属蛋白酶活性的表达与转移能力密切相关，这表明胶原酶IV活性和转移所需的其他特性在遗传上是相关联的。
