Fibroblasts stimulate human ovarian cancer cell invasion and expression of 72-kDa gelatinase A (MMP-2).
Fibroblasts stimulate human ovarian cancer cell invasion and expression of 72-kDa gelatinase A (MMP-2).
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DOI：
10.1006/gyno.1997.4808
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发表时间：
1997-10
影响因子：
4.7
通讯作者：
A. Westerlund;E. Hujanen;U. Puistola;T. Turpeenniemi‐Hujanen
中科院分区：
文献类型：
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作者：
A. Westerlund;E. Hujanen;U. Puistola;T. Turpeenniemi‐Hujanen
目的宿主-肿瘤相互作用和肿瘤基质可能参与调控肿瘤细胞的侵袭行为。为了更好地了解人类卵巢癌的侵袭，我们探索了正常成纤维细胞参与控制人类卵巢癌扩散的可能性。结果将正常成纤维细胞（CRL 1295）与肿瘤细胞一起加入到侵袭室时，人卵巢癌细胞（Ovcar-3）通过重组基底膜的侵袭性增加了3.5倍（从2.83 +/- 0.97增加到10.2 +/- 3.43%）。与未受刺激的对照细胞相比，来自成纤维细胞或Ovcar-3的条件培养基也使Ovcar-3的体外侵袭能力提高了2- 2.5倍（分别从2.83 +/- 0.97增加到5.71 +/- 3.5%和7.15 +/- 1.2%）。酶谱分析和72kda基质金属蛋白酶（MMP-2） mRNA的测定表明，Ovcar-3细胞单独产生极低水平的MMP-2；这种明胶酶的表达在酶谱上可以检测到，只有在这些细胞与来自成纤维细胞或卵巢癌细胞本身的条件培养基孵育的刺激下才能检测到。有趣的是,MMP-2活动增加也在成纤维细胞使用卵巢癌cell-conditioned(178 + / - 67%)或fibroblast-conditioned中等(215 + / - 61%)和MMP-2同样增加的基因表达Ovcar-3细胞和成纤维细胞在使用fibroblast-conditioned介质或卵巢癌cell-conditioned介质从1.00 + / - 0.25到2.20 + / - 0.50和1.86 + / - 0.10,成纤维细胞,从1.00 + / - 0.26到1.60 + / - 0.34和2.15 + / - 0.30 Ovcar-3细胞,分别。结论肿瘤细胞与正常细胞相互作用，控制蛋白水解酶的侵袭和分泌，可能不仅涉及旁分泌因素，还涉及自分泌因素。因此，这种相互作用是可能的，并且可能在癌症的扩散中发挥重要作用。
OBJECTIVE The host-tumor interactions and tumor stroma may participate in the regulation of invasive behavior of tumor cells. In order to better understand the human ovarian cancer invasion we explored the possibility that normal fibroblasts could participate in the control of the spread of human ovarian cancer. RESULTS A 3.5-fold increase (from 2.83 +/- 0.97 to 10.2 +/- 3.43%) in human ovarian cancer cell (Ovcar-3) invasion through a reconstituted basement membrane was noted when normal fibroblasts (CRL 1295) were added to the invasion chambers in conjunction with tumor cells. Conditioned medium from either fibroblasts or Ovcar-3 also enhanced the in vitro invasion of Ovcar-3 by 2- to 2.5-fold (from 2.83 +/- 0.97 to 5.71 +/- 3.5 and to 7.15 +/- 1.2%, respectively) compared to nonstimulated control cells. Zymographic analysis and assays of mRNA for the 72-kDa matrix metalloproteinase (MMP-2) showed that Ovcar-3 cells alone produced very low levels of MMP-2; the expression of this gelatinase was detectable in zymography only with stimulation by incubation of these cells with conditioned media from either fibroblasts or ovarian cancer cells themselves. Interestingly, MMP-2 activity was increased also in fibroblasts when using either ovarian cancer cell-conditioned (to 178 +/- 67%) or fibroblast-conditioned medium (to 215 +/- 61%) and the gene expression for MMP-2 was similarly increased in both fibroblasts and Ovcar-3 cells when using either fibroblast-conditioned medium or ovarian cancer cell-conditioned medium from 1.00 +/- 0.25 to 2.20 +/- 0.50 and 1.86 +/- 0.10 in fibroblasts and from 1.00 +/- 0.26 to 1.60 +/- 0.34 and 2.15 +/- 0.30 in Ovcar-3 cells, respectively. CONCLUSIONS These results show that interplay between tumor cells and normal cells in the control of invasion and secretion of proteolytic enzymes may involve not only paracrine but also autocrine elements. Thus, such interactions are possible and may play an important role in the spread of cancer.